Abstract
Heat stress (HS) can cause a series of stress responses, resulting in numerous negative effects on the body, such as the diminished food intake, carcass quality and reproductive capacity. In addition to the negative effects on the peripheral system, HS leads to central nervous system (CNS) disorders given its toll on neuroinflammation. This neuroinflammatory process is mainly mediated by microglia and astrocytes, which are involved in the activation of glial cells and the secretion of cytokines. While the regulation of inflammatory signaling has a close relationship with the expression of heat shock protein 70 (Hsp70), HS-induced neuroinflammation is closely related to the activation of the TLR4/NF-κB pathway. Moreover, oxidative stress and endoplasmic reticulum (ER) stress are key players in the development of neuroinflammation. Chromium (Cr) has been widely shown to have neuroprotective effects in both humans and animals, despite the lack of mechanistic evidence. Evidence has shown that Cr supplementation can increase the levels of insulin-like growth factor 1 (IGF-1), a major neurotrophic factor with anti-inflammatory and antioxidant effects. This review highlights recent advances in the attenuating effects and potential mechanisms of Cr-mediated IGF-1 actions on HS-induced neuroinflammation, providing presently existing evidence supporting the neuroprotective role of Cr.
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Introduction
In recent years, the rise in global temperature has posed great challenges to the health of humans and animals, with heat-related diseases gradually attracting the attention of researchers. Of note, high temperature environments cause great economic losses to animal husbandry production in many regions (Ebi et al. 2021; Goel 2021).
Heat stress (HS) represents the sum of systemic, non-specific reactions in animals present in high-temperature and high-humidity environments caused by insufficient heat dissipation and uncontrolled thermoregulation (Roenfeldt 1998). Under HS conditions, a series of pathophysiological responses, including high temperature, reduction of feed intake, dehydration, dyspnea, increased heart rate and gastrointestinal injuries, may emerge prominently (Vargas and Marino 2016; Chen et al. 2021a, b). Notably, due to the activation of the hypothalamic–pituitary–adrenal (HPA) axis and increased production of glucocorticoids, HS causes an inhibitory effect on the immune system (Bagath et al. 2019). In addition, HS is detrimental to the reproductive capacity and product quality of animals. In fact, it may cause bull lower semen quality (Morrell 2020), decreased milk of dairy cows (Tao et al. 2020) and egg production of laying hens (Li et al. 2020), and the development of pale, soft and exudative (PSE) meat in acute HS or dark, firm and dry (DFD) meat in chronic HS in pigs (Gonzalez-Rivas et al. 2020).
Moreover, in the central nervous system (CNS), HS can lead to many neurological disorders due to its highly inflammatory conditions. Neuroinflammation refers to the inflammation in the CNS (especially brain tissue), which can be triggered by noxious stimuli and conditions, including HS (Medzhitov 2008; Lee et al. 2015; Chauhan et al. 2017; Zhao et al. 2021a, b). Acute inflammation may have a protective effect on animals (e.g., providing protection against infections or promoting tissue repair and angiogenesis) (Aggarwal et al. 2006; Varin and Gordon 2009). However, when inflammation becomes chronic, it is highly detrimental to brain tissue, often causing synaptic dysfunction, inhibition of neurogenesis, neuronal death and cognitive impairment (Lyman et al. 2014).
Chromium (Cr) is a promising agent against the adverse effects of HS in animals (Bin-Jumah et al. 2020). Cr acts as a second messenger and amplifies insulin signals, which facilitates the role of insulin neuromodulation (Vincent 2015; Nakabeppu 2019). Evidence suggests that Cr has positive effects on the brain, namely improving cognitive function in the elderly and ameliorating depression (Krikorian et al. 2010; Andrieux et al. 2021). Importantly, the anti-inflammatory and antioxidant effects as well as the modulation of insulin-like growth factor 1 (IGF-1) signaling of Cr supplements are well-recognized (Peng et al. 2010; Chen et al. 2014; Ullah Khan et al. 2014; Morvaridzadeh et al. 2022). Therefore, in this article, we addressed the mechanisms underlying HS-induced neuroinflammation and explored the link between Cr and IGF-1 signaling, further unraveling the potential role of Cr-mediated IGF-1 in inhibiting neuroinflammation induced by HS.
HS effects on the CNS and neuroinflammation
To the best of our knowledge, the brain is extremely sensitive to high temperature, with both structure and function being damaged by HS (Walter and Carraretto 2016). Previous studies suggest that HS can induce brain perfusion reduction and CNS fatigue, destroy the integrity of the blood–brain barrier (BBB) and cause brain edema, leading to modifications in neuronal circuits, neurological defects, spasms and even brain atrophy (Sharma et al. 1998; Nybo 2007). Moreover, a multitude of pathological processes can be observed by magnetic resonance imaging (MRI) in the heat-stressed CNS, such as hemorrhage, edema, ischemia, and encephalitis (Zhang and Li 2014; Li et al. 2015). Based on these pathological processes, animals under HS may suffer severe CNS dysfunction including combativeness, delirium, seizures, and coma (Fig. 1) (Bouchama and Knochel 2002).
Negative effects of HS on the CNS. HS can destroy the integrity of the BBB and cause brain edema, and can induce brain hemorrhage, ischemia and neuroinflammation, which lead to CNS dysfunction. In addition, severe neuroinflammation contributes to the development of brain pathology, such as thermoregulatory dysfunction, neurogenesis impairment and neurodegeneration
In addition, neuroinflammation caused by HS is likely a key mechanism underlying the development of brain pathology. For example, Chauhan et al. have previously indicated that the main cause of thermoregulatory dysfunction under HS conditions is associated with abnormal monoamine levels in the hypothalamus caused by neuroinflammation (Chauhan et al. 2017). Moreover, inflammation in the heat-stressed hypothalamus was found to exacerbate neurodegeneration and brain damage (Moon et al. 2017). Similarly, in the inflammatory-targeted hippocampus, HS was shown to display negative effects on adult neurogenesis and cognitive function (Lee et al. 2015; Zhu et al. 2023). More importantly, prolonged neuroinflammation can lead to various neurological disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD) (Niranjan 2018). Hence, given the significance of preventing neuroinflammation-induced neurodegeneration, one needs to further explore the actions of appropriate neuroprotective drugs in different conditions.
Chromium-mediated neuroprotection
Minerals, and specifically Cr, are vital nutrients for humans and animals to maintain and facilitate physical health. Although Cr is not an essential element, according to new evidence and a report released by the European Food Safety Authority, its pharmacological activity has been extensively studied (Vincent 2014, 2017). Cr exists mainly in two oxidized forms in nature: trivalent (Cr (III)) and hexavalent (Cr (VI)). While Cr (VI) is a recognized human carcinogen and has been shown to be neurotoxic (Wang et al. 2011; Singh and Chowdhuri 2017), accumulating evidence shows that Cr (III) can be used as a dietary supplement. Acting as a component of the glucose tolerance factor, Cr is important for enhancing the effect of insulin (Siddiqui et al. 2014). Therefore, given its relevance in improving carbohydrate and lipid metabolism, it is commonly used in research addressing treatments for diabetes and obesity in humans and animal models (Vincent 2001; Tian et al. 2013; Maret 2019; Wo et al. 2023). Recently, dietary Cr supplementation is becoming widely used in livestock husbandry with the aim of improving growth performance, production capacity, immune function, and antioxidative ability (Zheng et al. 2016; Sahin et al. 2017; Bin-Jumah et al. 2020; Bompadre et al. 2020; Piray and Foroutanifar 2021). Moreover, several studies are emerging on the protective effect of Cr to the brain. Dietary supplementation of Cr was shown to alleviate post-stroke brain infarction and hyperglycemia in rats (Chen et al. 2016). Oral Cr administration was found to increase concentrations of 5-hydroxytryptamine and tryptophan in the serum and brain, improving neurological function in terms of learning and memory (Orhan et al. 2017). More importantly, in depression, a condition extremely harmful to people's mental health, the administration of low-dose antidepressants supplemented with Cr was found to be an effective mitigation method (Młyniec et al. 2014; Khodavirdipour et al. 2020).
The study on the neuroprotective mechanisms of Cr has attracted the attention of many scientists because of its beneficial effects on CNS pathophysiology. Its main mechanisms of action include increased insulin sensitivity in the brain (Krikorian et al. 2010) and anti-inflammatory and antioxidant effects (Sahin et al. 2010; Akhtar et al. 2020). As a second messenger, Cr is responsible for expanding insulin signal transduction, further enhancing its role in metabolism (Vincent 2015). Brain insulin plays a vital role in regulating both systemic metabolism and brain function, being involved in feeding, depression, cognitive behavior, and energy homeostasis (Agrawal et al. 2021; Schell et al. 2021). Moreover, insulin is also involved in the maintenance of protein homeostasis, affecting the clearance of amyloid β (Aβ) peptide and the phosphorylation of tau, both known AD protein markers (Kellar and Craft 2020). Hence, when insulin resistance — defined as a reduced efficiency of insulin in promoting glucose uptake and utilization — occurs, the brain and systemic energy metabolism is disrupted and neurodegeneration may be induced (Lebovitz 2001; Sędzikowska and Szablewski 2021). It is particularly essential to supplement certain drugs in this period, namely with Cr, to increase insulin sensitivity. Additionally, Cr attenuates neuroinflammation by reducing pro-inflammatory cytokines levels such as tumor necrosis factor α (TNF-α) and interleukin (IL)-6 and enhances the ability of the antioxidant system to reduce oxidative stress (Sahin et al. 2012; Akhtar et al. 2020). However, the neuroprotective effects of Cr have not yet been fully covered. The insulin-related peptide IGF-1 also plays a role in maintaining the internal homeostasis of the brain (Song et al. 2016). Recent experimental evidence has shown that, under HS conditions, Cr supplementation can significantly increase serum concentrations of IGF-1 (Zha et al. 2009). Therefore, one may speculate that the neuroprotective effects of Cr may engage IGF-1 signaling.
Chromium and IGF-1
IGF-1 is an anabolic hormone that plays an important role in facilitating cell proliferation, dilating blood vessels and maintaining muscle mass and strength (Obradovic et al. 2019; Yoshida and Delafontaine 2020). IGF-1 is synthesized in the liver and enters nerve tissues through the BBB or cerebrospinal fluid in the choroid plexus (Carro and Torres-Aleman 2006). Interestingly, Cr appears to be involved in the nutritional regulation of IGF-1 levels and bioactivity. In skeletal muscle cells, Cr improves protein deposition by up-regulating mRNA levels of IGF-1 and IGF-1 receptor (IGF-1R) (Peng et al. 2010). Similarly, in pigs, increased IGF-1 levels due to Cr-supplemented diets were shown to play a role in regulating protein and fat metabolism (Wang et al. 2014). Contrastingly, in rats, maternal Cr consumption leads to decreased fetal IGF-1 concentrations, which may have negative effects on fetal protein levels and growth (Spicer et al. 1998). Moreover, Cheng et al. found that offspring of Cr-treated male mice display increased IGF-1 serum levels (Cheng et al. 2002). Despite the lack of mechanistic evidence, these results suggest a potential link between Cr and IGF-1 levels.
Given their role as growth factors, both IGF-1 and growth hormone (GH) exert neurotrophic and neuroregenerative actions (Bianchi et al. 2017). Therefore, the regulation of Cr on the biological activity of the GH-IGF-1 axis should also be noted. For instance, a Cr nanocomposite was found to enhance the mRNA expression and secretion of GH, facilitating the growth of finishing pigs (Wang et al. 2009). In contrast, in another experiment, finishing pigs treated with Cr methionine showed a decline in GH and IGF-1 levels (Tian et al. 2014). One possible explanation for these opposing differences may be the different forms of Cr supplementation. Hence, the potential link between Cr and IGF-1, supported by increased GH levels with Cr supplementation, is yet to be established and requires further research. Evidence suggests that Cr may attenuate neuroinflammation through anti-inflammatory and antioxidant effects (Akhtar et al. 2020) and the regulation of glial cells activity (Sahin et al. 2013), as does IGF-1 (Higashi et al. 2010; Labandeira-Garcia et al. 2017). Based on the effects of Cr on IGF-1 levels and IGF-1 signaling, we further discussed the mechanism of IGF-1 in suppressing neuroinflammation to explain the potential anti-neuroinflammation of Cr.
Potential attenuating effects of IGF-1 on HS-induced neuroinflammation
As a bioactive hormone, the expression levels and function of IGF-1 are susceptible to the effects of HS. In this regard, serum insulin, IGF-1, and glucose levels were found to be decreased in summer compared to winter in dairy cattle, possibly due to low dry matter intake and elevated negative energy balance (Hammond et al. 1990; Jonsson et al. 1997; Shehab-El-Deen et al. 2010). For animals suffering from HS, IGF-1 has protective effects on various tissues. Evidence indicates that, as the main targets of heat-stressed animals, oocytes supplemented with physiological concentrations of IGF-1 have been shown to have increased heat resistance, reduced reactive oxygen species (ROS) production and lowered rate of apoptosis (Rodrigues et al. 2016; Ascari et al. 2017; Lima et al. 2017). In all types of cells in the CNS, microglia are the main source of IGF-1 expression, and IGF-1R are preponderantly expressed in neurons and astrocytes (Labandeira-Garcia et al. 2017). When IGF-1 binds to its receptor, two major signaling pathways are activated: the mitogen-activated protein kinase (MAPK) pathway and the phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT) pathway, both having critical effects on IGF-1-induced cell growth, survival, migration and proliferation (Yin et al. 2017). Importantly, its role as a neurotrophic hormone enables brain development and maturation, neuroplasticity and peripheral neuroregeneration (Rabinovsky 2004; Dyer et al. 2016; Zorina et al. 2023). IGF-1 maintains the integrity of the BBB, which is known to decline gradually during aging (Bake et al. 2016). In a rat model of ischemic stroke, systemic injection of IGF-1 promoted a 50% reduction in cerebral infarction size by binding to IGF-1R (De Geyter et al. 2016). In conditions of heat-stressed CNS, the disruption of IGF-1 signaling was shown to weaken the clearance of Aβ, which may mediate the development of neuroinflammation and neurodegeneration (Urban et al. 2012). On the other hand, chronic inflammation, in turn, was found to exacerbate insulin/IGF-1 signaling defects in the brain (Spielman et al. 2014). Hence, under HS conditions, IGF-1 signaling plays a critical regulatory role in the innate immune response and brain pathophysiology.
IGF-1 and microglia-mediated neuroinflammation
Microglia, the resident immune cells in the CNS, are the first immune defense line of the CNS, being responsible for protecting CNS from damage and pathogen invasion. In the homeostatic brain tissue, microglia are essential facilitators of neuronal development and promoters of brain health through the secretion of trophic factors (Nayak et al. 2014). Microglia are also involved in synaptic pruning, which is highly related to cognitive function and the establishment of functional neural networks (Paolicelli et al. 2011). Contrarily, some evidence shows that overactivated microglia possess neurotoxic activity, causing neurodegeneration in the case of chronic neuroinflammation (Lindhout et al. 2021). According to their morphology, microglia are classified in three main types: resting ramified, activated, and amoeboid phagocytic (Ling and Wong 1993). Regardless of their morphological state, they perform monitoring functions by sensing changes in the microenvironment through their highly moving protrusions, a phenomenon more frequent in the resting ramified state (Nimmerjahn et al. 2005).
One of the most striking features of microglia is that when they receive internal signals (e.g., stress) or external signals (e.g., pathogen), they will become activated and transform from resting ramified cells into amoeboid phagocytic cells (Aloisi 2001). This activation is of multiplicity, depending on the source of stress and the type of pathology. According to the different phenotypic characteristics and functions, activated microglia can be divided into M1 and M2 polarization types. M1 microglia can release pro-inflammatory cytokines under the stimulation of lipopolysaccharide (LPS) or interferon-γ (IFN-γ), serving as the first line of defense of the innate immune system (Orihuela et al. 2016). M2 microglia stimulated by IL-4 or IL-13 can be competent in anti-inflammation and neuroprotection (Orihuela et al. 2016). Increasing evidence has been reported that, under HS conditions, the activity of M1 microglia is increased, promoting the production of pro-inflammatory mediators, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α and IL-6 (Vezzani and Ruegg 2011; Estes and McAllister 2014; Lyman et al. 2014; Hsuan et al. 2016). Moreover, Weninger et al. found that, in hippocampal slices treated with a heat shock, the number of microglia significantly increased, based on Iba-1 positive staining, when compared with the control group, with an abundant number of actively phagocytic microglia being observed (Weninger et al. 2021). Similar results were reported in the hypothalamus during acute HS (Belity et al. 2022). Therefore, HS can induce the activation and proliferation of microglia, which may trigger neuroinflammation. Accordingly, an in-depth understanding of changes in the microglial state is of great significance for neuroinflammation.
Activation of microglia is the first and most critical step in neuroinflammation. IGF-1 is a mitogen for microglia that can also function as a regulator of microglial polarization to modulate microglia-mediated neuroinflammation (Fig. 2) (Labandeira-Garcia et al. 2017). In addition, IGF-1/IGF-1R signaling transduction is vital for regulating microglia morphology and transcriptome, which reduces the severity of inflammatory response (Ivan et al. 2023). As a marker of the M2 phenotype, IGF-1 was shown to promote CD206 expression in mice with intracerebral hemorrhage, accompanied by elevated levels of anti-inflammation mediators such as IL-10 and transforming growth factor β (TGF-β) (Sun et al. 2020). The expression levels of arginase-1, another enzyme associated with an anti-inflammatory microglia phenotype, were found to be increased after IGF-1 overexpression (Falomir-Lockhart et al. 2022). In addition, novel insights into the regulation of mitochondrial metabolism and autophagy on microglial polarization have emerged (Orihuela et al. 2016; Jiang et al. 2020). Indeed, Ji et al. confirmed that IGF-1 facilitated a M1-to-M2 shift of microglia by enhancing autophagy (Ji et al. 2018). Ferger et al. suggested that mitochondrial dysfunction inhibited a M2 microglia phenotype induced by IL-4 (Ferger et al. 2010). Hence, according to these pieces of evidence, perhaps IGF-1 is promoting the transformation of microglia to a M2 phenotype to alleviate neuroinflammation through the improvement of mitochondrial function (Sadaba et al. 2016; Yang et al. 2021). Furthermore, IGF-1 exhibited anti-inflammatory effects by reducing LPS-induced expression of brain inflammatory factors through the downregulation of microglia activation and production of endogenous growth factors (Sukhanov et al. 2007; Park et al. 2011a, b; Tien et al. 2017). In senile rats (Falomir-Lockhart et al. 2019) and traumatic intracerebral hemorrhage models (Herrera et al. 2021), IGF-1 gene therapy was also found to modulate the proliferation of reactive microglia. Taken together, multiple pieces of evidence indicates that a strict regulation of IGF-1 levels is essential for the modulation of microglial inflammatory responses in the CNS, which provides a reference for exploring the regulation of Cr on the activity of microglia.
IGF-1 and astrocytes-mediated neuroinflammation
Astrocytes are abundant glial cells in the brain tissue and perform complex and diverse functions, including nutrient supply to neurons, synaptic integrity maintenance, and regulation of local CNS blood volume (Ransom et al. 2003). Astrocytes become activated in response to various adverse stimuli, a process defined by increased expression of glial fibrillary acidic protein (GFAP) (Sofroniew 2009). After activation, astrocytes release pro-inflammatory signaling molecules, particularly in the cortex and midbrain, in order to build up responses to innate immune triggers (Kipp et al. 2008). In addition to their pro-inflammatory role, it has been demonstrated that cytotoxic molecules secreted by astrocytes greatly contribute to neurodegenerative pathophysiology, especially in AD (Liddelow et al. 2017; Li et al. 2019a, b). Another way in which astrocytes respond to various forms of CNS damage is the double-edged sword process of reactive astrogliosis. On the one hand, glial scars formed during severe reactive astrogliosis have neuroprotective effects that limit the spread of inflammation and pathogens (Sofroniew and Vinters 2010). On the other hand, loss of physiological function or gain of adverse effects of reactive astrocytes may be the pathological basis of CNS dysfunction, such as trauma and stroke (Sofroniew 2009). Accumulating evidence indicates that acute HS can induce increased expression of reactive astrocytes actively involved in different pathophysiological processes in a short period of time (Sharma et al. 1992; Moon et al. 2017). In fact, frequent repetitive thermal stimulation to the hippocampus was shown to prolong the activation time of astrocytes concomitant with increased expression of GFAP (Yang et al. 2009). In addition, Chauhan et al. discovered that severe HS promotes an increased expression of GFAP in the hypothalamus accompanied by inflammation (Chauhan et al. 2017). In conclusion, astrocytes can also become activated and proliferate, contributing to the secretion of pro-inflammatory cytokines and chemokines that induce inflammation (Banjara and Ghosh 2017).
Evidence has shown that IGF-1 plays a vital role in regulating astrocytic activity (Fig. 2) (Labandeira-Garcia et al. 2017). According to Fernandez et al., further investigation on the regulation of astrocyte function by IGF-1 is essential to fully understanding the biological role of IGF-1 in the brain (Fernandez et al. 2007). The modulation mediated by IGF-1 on mitochondrial dynamics and the redox state of astrocytes is important for astrocyte function (Logan et al. 2018). IGF-1 regulates the energy supply of the brain by promoting astrocytic glucose uptake (Hernandez-Garzón et al. 2016). Severely, mice lacking IGF-1R in astrocytes show cognitive impairment, which is related to the development of the AD-like pathology (Zegarra-Valdivia et al. 2022). In addition, IGF-1 targeting astrocytes-mediated neuroinflammation is a crucial part of its neuroprotective effects. When astrocytes are exposed to IGF-1 for a long time, sustained activation of IGF-1R will inhibit astrocytic mitosis through the upregulation of phosphatase and tensin homolog deleted on chromosome ten (PTEN) activity (Fernandez et al. 2007). Accumulating reports also show that IGF-1 is able to reduce the number of GFAP-positive astrocytes in aging and nerve injury models (Miltiadous et al. 2011, Park et al. 2011a, b, Arroba and Valverde Á 2015, Okoreeh et al. 2017), which is similar with a Cr-induced GFAP fall in hypoglycemic rats (Sahin et al. 2013). In line with this, reactive astrocytes play an active anti-inflammatory role under the actions of IGF-1, suppressing the expression of pro-inflammatory cytokines and enhancing the secretion of neuroprotective factors (Fernandez et al. 2007). Recent experimental evidence indicates that an IGF-1 gene therapy effectively controlled reactive astrogliosis and attenuated astrocyte-mediated neuroinflammation induced by LPS (Bellini et al. 2011; Pardo et al. 2016). Nonetheless, given the two opposing facets of reactive astrogliosis, further discussion is needed on the role of IGF-1 in the regulation of astrocytic activity.
IGF-1 inhibits signaling pathways involved in neuroinflammation
In the CNS, heat shock proteins (Hsps) are highly conserved proteins synthesized by glial cells in response to HS (Taylor et al. 2007). Hsps act as molecular chaperones that promote the proper folding of nascent polypeptides and the repair of damaged proteins, playing a vital role in maintaining protein homeostasis. Oligodendrocytes are myelin-forming cells in the CNS that have been shown to provide nutrients to neurons (Kipp 2020). Nevertheless, under HS conditions, oligodendrocytes seem to play a neuroinflammatory role. Pavlik et al. found that oligodendrocytes, but not microglia and astrocytes, are major producers of Hsp70, the most ubiquitous and conserved Hsp, in rats subjected to heat-stressed conditions with circulating hot air (41.5℃) (Pavlik et al. 2003). Likewise, several reports have revealed that HS can induce increased expression of Hsp70 in the brain tissue (Moon et al. 2017; Kim et al. 2019). When extracellular Hsp70 binds to its receptor, a specific inflammatory signaling pathway is initiated (Dukay et al. 2019). Indeed, Hsp70 is an ideal damage-associated molecular pattern (DAMP) recognized by Toll-like receptor 4 (TLR4) that is highly conserved and significantly increased after HS (Dukay et al. 2019). TLR4 is mainly expressed on the membrane of microglia and astrocytes in nerve tissues, being a key receptor that contributes to the induction of inflammation and antiviral cytokines (Kumar 2019; Li et al. 2019a, b). After the binding of extracellular Hsp70 to TLR4, activated TLR4 induces the recruitment of downstream adaptors that lead to the activation of nuclear factor-kappa B (NF-κB) (Kawai and Akira 2010). Next, a large number of pro-inflammatory mediators are produced that accelerate neuroinflammation development (Kagan and Medzhitov 2006; Kim and Yenari 2013; Banjara and Ghosh 2017). Hence, there is not only a close relationship between the regulation of inflammatory signaling with Hsp70 expression but also between HS-induced neuroinflammation and the activation of the TLR4/NF-κB pathway.
Elevated Hsp70 expression is thought to reflect the response of nerve cells to stress and injury, which can eventually lead to neuroinflammation (Lee et al. 2000; Akbar et al. 2001; Giuliano et al. 2011). Kazanis et al. found that IGF-1 suppresses Hsp70 expression in the brain injury area, contributing to the alleviation of neuronal degeneration and death (Kazanis et al. 2003). Similar results were reported in the neurotoxic substance-induced hippocampal degeneration model (Miltiadous et al. 2010). Therefore, IGF-1 attenuates tissue overreaction to injury by reducing Hsp70 production. Notably, the anti-inflammatory effect of IGF-1 is known to be related to the inhibition of the TLR4/NF-κB pathway. In pathological processes such as lung injury (Munoz et al. 2021), cirrhosis (Zhao et al. 2021a, b), and enteritis (Tian et al. 2017), it has been demonstrated that IGF-1 inhibits the activation of the TLR4/NF-κB pathway, impeding cell damage and enhancing tissue repair. A study by Lee and colleagues indicated that the negative regulation of IGF-1 on TLR4 expression is highly associated with the PI3K/AKT pathway and the decreased expression of many NF-κB-mediated pro-inflammatory factors (e.g., TNF-α, IL-6) (Lee 2011). Moreover, recent evidence confirmed that IGF-1 has the ability to downregulate the expression of TLR4 and to mediate the inactivation of NF-κB by activating the PI3K/AKT pathway to reduce the astrocytic inflammatory response (Pinto-Benito et al. 2022). Moreover, IGF-1 can promote M2 microglial polarization via the inhibition of TLR4/NF-κB signaling transduction and lead to the elevation of neuroprotection factors such as IL-10 and TGF-β to attenuate microglia-mediated inflammation (Sun et al. 2020). Importantly, the reduced Hsp70 production and the inhibition of TLR4/ NF-κB pathway can be achieve by Cr supplement (Zhang et al. 2014; Kumar et al. 2015). The inhibitory effects of Cr and IGF-1 on inflammatory signaling pathways greatly facilitate the control or resolution of inflammation, providing compelling perspectives on the neuroprotective role of IGF-1 and the potential between Cr and IGF-1.
IGF-1 and oxidative stress
Mitochondria are not only the energy production center of cells but also the center of pro-inflammatory responses (Andrieux et al. 2021). HS is a known inducer of mitochondrial dysfunction in rat CNS neurons and can lead to a decreased ability to neutralize or to the overproduction of ROS (White et al. 2012). Additionally, NADPH oxidases (NOX) like NOX-1 and NOX-4 are involved in ROS production under HS conditions (Moon et al. 2010; Kikusato et al. 2015). To prevent cells from oxidative damage, mitochondria have an antioxidative defense capability. However, HS inhibits the total antioxidant capacity (T-AOC), which is characterized by the presence of glutathione and enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and hemeoxygenase-1 (HO-1) (Liu et al. 2016; Wang et al. 2019; Chauhan et al. 2021; Oghbaei et al. 2021). Moreover, the concentration of malondialdehyde (MDA), an indicator of lipid peroxidation, has been shown to be increased in the diencephalon of chicks exposed to heat (Chowdhury et al. 2014). Collectively, HS induces the excessive production of ROS and reduces the antioxidative capacity of the system, resulting in oxidative damage. Oxidative stress is a crucial potential factor of inflammatory responses. ROS accelerate the recruitment of inflammatory cells and increase the expression of cytokines and chemokines by activating different transcription factors, including NF-κB (Guzik et al. 2003; Kim et al. 2013; Ding et al. 2020; Eckert et al. 2021). In the brain tissue, ROS induce inflammation and neuron death, which in turn mediates neurodegeneration and memory loss (Popa-Wagner et al. 2013).
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a sensor and transcriptional mediator of antioxidants and oxidative signals, being a great preventor of oxidative damage (Ma et al. 2006). After the activation of Nrf2, it can be transferred into the nucleus, where it binds to the antioxidative response element (ARE), initiating a downstream pathway for signal transduction that promotes the synthesis of enzymatic antioxidants, including SOD, CAT, and HO-1 (Jung and Kwak 2010). Recent experimental evidence has shown that increased levels of IGF-1 prevent renal cells against oxidative damage induced by cisplatin (Mahran 2020). In addition, IGF-1/IGF-1R signaling in the brain was found to activate the Nrf2/HO-1 pathway, an important antioxidant and anti-inflammatory pathway (Kim et al. 2012; Luo et al. 2017; Ma et al. 2020; Niu et al. 2020), and Cr plays an antioxidative role through enhancing the Nrf2 activity and the antioxidants expression levels (Sahin et al. 2017; Chen et al. 2021a, b). According to Wang et al., IGF-1 protects SH-SY5Y cells against Aβ-induced cell injury by reducing ROS through the PI3K/Akt-Nrf2 signaling pathway in an AD model (Wang et al. 2017). Similarly, Sui et al. reported that IGF-1 improved tau pathology induced by high-fat diet via the activation of the Nrf2/HO-1 signaling pathway (Sui et al. 2021). Moreover, knockdown of IGF-1 was shown to reduce antioxidant defenses by impairing the Nrf2-dependent antioxidant response (Bailey-Downs et al. 2012). Collectively, Nrf2/HO-1 is an important antioxidative pathway that mediates Cr and IGF-1 actions. Furthermore, increasing evidence now suggests that low doses of IGF-1's can effectively ameliorate mitochondrial dysfunction, resulting in reduced ROS production, oxidative damage and apoptosis, and in an elevation of ATP production (Puche et al. 2008; Sadaba et al. 2016; Yang et al. 2021; Lv et al. 2022). These conclusions suggest that IGF-1 can ameliorate mitochondrial dysfunction and enhance the function of the antioxidant defense system to neutralize or scavenge the excessive production of ROS induced by HS.
IGF-1 and endoplasmic reticulum stress
Endoplasmic reticulum (ER) is an important organelle responsible for protein synthesis in cells and plays a critical role in assisting protein modification and folding (Gong et al. 2017). Aggregation of unfolded or misfolded proteins in ER under adverse conditions leads to ER stress. Signal transduction of unfolded proteins depends on three resident transmembrane proteins on the endoplasmic reticulum membrane: inositol-requiring enzyme 1α (IRE1α), pancreatic endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) (Chandrika et al. 2015; Oakes and Papa 2015). As classical markers of ER stress, glucose-regulated protein 78 (GRP78) and C/EBP-homologous protein (CHOP) expression levels are increased under HS conditions (Dong et al. 2017). Furthermore, excessive production of ROS may disrupt ER homeostasis by aggravating oxidative damage (Zhang et al. 2016). Compelling evidence now demonstrates that ER stress can induce the activation of microglia, astrocytes and NF-κB, representing a key step in the development of neuroinflammation (Meares et al. 2014; Harvey et al. 2015; Sprenkle et al. 2017). Other lines of evidence indicate that HS increases the levels of misfolded proteins, resulting in ER-triggered apoptosis (Chen et al. 2008; Nasrolahi et al. 2020). Moreover, ER stress was found to inhibit the transcription of the IGF-1 gene, resulting in decreased IGF-1 sera and brain tissue levels (Marwarha et al. 2016; Xia et al. 2020). However, IGF-1 seems to be a new target for reducing ER stress in the CNS. Recent experimental results showed that in fibroblasts the increased expression levels of IGF-1 inhibited the expression of ER stress-related genes (Di Patria et al. 2022). According to Fang et al., under high glucose conditions, IGF-1 alleviates ER stress and ER stress-induced apoptosis in rat gastric smooth muscle cells (Fang et al. 2019). Furthermore, IGF-1 was found to enhance the expression of CHOP and to inhibit the phosphorylation of eIF2α, thus attenuating 6-OHDA-induced ER stress-mediated apoptosis in PC-12 neuronal cells (Kim et al. 2012). Before that, Zou et al. reported that IGF-1 effectively protected PC-12 neuronal cells against ER stress-induced apoptosis through the PI3K/Akt and p38 MAPK pathways(Zou et al. 2009). In addition, gestational diabetes rats with Cr supplement showed that the reduced GRP78 level and IRE1α activity can prevent liver from ER stress (Yao et al. 2021). Hence, the abovementioned evidence suggests that Cr and IGF-1 play positive roles in inhibiting HS-induced ER stress, which provides prospective about Cr promoting IGF-1 actions.
Conclusion
With global warming, the frequency of HS increases, and its adverse effects on the CNS cannot be ignored. As demonstrated in this present review, HS can activate glial cells and the NF-κB pathway to facilitate the production of pro-inflammatory cytokines that lead to neuroinflammation. Moreover, HS-induced oxidative stress and ER stress further contribute to the development of neuroinflammation, cell death and tissue damage. If inflammation becomes unmanageable, it may lead to several neurological diseases that greatly threaten and harm the normal lives of animals. Cr, an important mineral present in nature, has been shown to play an important anti-inflammatory and antioxidant role in the brain. Interestingly, elevated production of IGF-1 is induced by the supplementation with Cr. As a neuroprotective factor, IGF-1 mediates the anti-inflammatory effects of microglia and astrocytes. In addition, IGF-1 decreases Hsp70 levels and inhibits the activation of the TLR4/NF-κB pathway to suppress the expression of pro-inflammatory cytokines. Moreover, IGF-1 attenuates oxidative stress and ER stress via the PI3K/Akt pathway to ameliorate cell damage. Therefore, one can conclude that Cr efficiently ameliorates neuroinflammation evoked by HS through the mediation of IGF-1 signaling (Fig. 3). Considering the putative pro-inflammatory effects of IGF-1 in other backgrounds, further experiments focused on HS are needed to verify this hypothesis. The findings of these upcoming studies will create the rationale for an effective approach in the prevention and treatment of neurological diseases associated with HS.
Cr attenuates HS-induced neuroinflammation via the neuroprotective effects of IGF-1. HS induces the proliferation of microglia and astrocytes, which can be inhibited by Cr-induced IGF-1. Under HS conditions, when Hsp70 binds to TLR4, the NF-κB is activated to facilitate the expression of pro-inflammatory factors. This can also happen after oxidative stress and ER stress, leading to neuroinflammation. Cr supplementation can increase IGF-1 levels which, in turn, suppress the expression of Hsp70. After the binding of IGF-1 to IGF-1R, the PI3K/Akt pathway is activated, which inhibits the activation of the TLR4/NF-κB signaling transduction to reduce the expression of pro-inflammatory factors. Moreover, IGF-1 enhances antioxidative defense via the PI3K/Akt-Nrf2/HO-1 pathway to clear the excessive production of ROS. Additionally, through PI3K/Akt pathway, IGF-1 ameliorates ER stress to prevent the apoptosis of neuronal cells
Availability of data and materials
Not applicable.
Abbreviations
- ATF6:
-
Activating transcription factor 6
- AD:
-
Alzheimer's disease
- Aβ:
-
Amyloid β
- BBB:
-
Blood-brain barrier
- CHOP:
-
C/EBP-homologous protein
- CAT:
-
Catalase
- CNS:
-
Central nervous system
- Cr:
-
Chromium
- COX:
-
Cyclooxygenase
- DAMP:
-
Damage-associated molecular pattern
- ER:
-
Endoplasmic reticulum
- GFAP:
-
Glial fibrillary acidic protein
- GRP78:
-
Glucose-regulated protein 78
- GPx:
-
Glutathione peroxidase
- GH:
-
Growth hormone
- Hsp70:
-
Heat shock protein 70
- HS:
-
Heat stress
- HO-1:
-
Hemeoxygenase-1
- iNOS:
-
Inducible nitric oxide synthase
- IRE1α:
-
Inositol-requiring enzyme 1α
- IGF-1:
-
Insulin-like growth factor 1
- IGF-1R:
-
Insulin-like growth factor 1 receptor
- IFN:
-
Interferon
- IL:
-
Interleukin
- LPS:
-
Lipopolysaccharide
- MDA:
-
Malondialdehyde
- MAPK:
-
Mitogen-activated protein kinase
- Nrf2:
-
Nuclear factor erythroid 2-related factor 2
- NF-κB:
-
Nuclear factor-kappa B
- PEPK:
-
Pancreatic endoplasmic reticulum kinase
- PI3K:
-
Phosphatidyl inositol 3-kinase
- AKT:
-
Protein kinase B
- ROS:
-
Reactive oxygen species
- SOD:
-
Superoxide dismutase
- TLR4:
-
Toll-like receptor
- T-AOC:
-
Total antioxidant capacity
- TGF:
-
Transforming growth factor
- TNF:
-
Tumor necrosis factor
References
Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G (2006) Inflammation and cancer: how hot is the link? Biochem Pharmacol 72:1605–1621. https://doi.org/10.1016/j.bcp.2006.06.029
Agrawal R, Reno CM, Sharma S, Christensen C, Huang Y, Fisher SJ (2021) Insulin action in the brain regulates both central and peripheral functions. Am J Physiol Endocrinol Metab 321:E156-e163. https://doi.org/10.1152/ajpendo.00642.2020
Akbar MT, Wells DJ, Latchman DS, de Belleroche J (2001) Heat shock protein 27 shows a distinctive widespread spatial and temporal pattern of induction in CNS glial and neuronal cells compared to heat shock protein 70 and caspase 3 following kainate administration. Brain Res Mol Brain Res 93:148–163. https://doi.org/10.1016/s0169-328x(01)00199-1
Akhtar A, Dhaliwal J, Saroj P, Uniyal A, Bishnoi M, Sah SP (2020) Chromium picolinate attenuates cognitive deficit in ICV-STZ rat paradigm of sporadic Alzheimer’s-like dementia via targeting neuroinflammatory and IRS-1/PI3K/AKT/GSK-3beta pathway. Inflammopharmacology 28:385–400. https://doi.org/10.1007/s10787-019-00681-7
Aloisi F (2001) Immune function of microglia. Glia 36:165–179. https://doi.org/10.1002/glia.1106
Andrieux P, Chevillard C, Cunha-Neto E, Nunes JPS (2021) Mitochondria as a Cellular Hub in Infection and Inflammation. Int J Mol Sci 22. https://doi.org/10.3390/ijms222111338
Arroba AIM, Valverde Á (2015) Inhibition of Protein Tyrosine Phosphatase 1B Improves IGF-I Receptor Signaling and Protects Against Inflammation-Induced Gliosis in the Retina. Invest Ophthalmol Vis Sci 56:8031–8044. https://doi.org/10.1167/iovs.15-17234
Ascari IJ, Alves NG, Jasmin J, Lima RR, Quintão CCR, Oberlender G, Moraes EA, Camargo LSA (2017) Addition of insulin-like growth factor I to the maturation medium of bovine oocytes subjected to heat shock: effects on the production of reactive oxygen species, mitochondrial activity and oocyte competence. Domest Anim Endocrinol 60:50–60. https://doi.org/10.1016/j.domaniend.2017.03.003
Bagath M, Krishnan G, Devaraj C, Rashamol VP, Pragna P, Lees AM, Sejian V (2019) The impact of heat stress on the immune system in dairy cattle: A review. Res Vet Sci 126:94–102. https://doi.org/10.1016/j.rvsc.2019.08.011
Bailey-Downs LC, Mitschelen M, Sosnowska D, Toth P, Pinto JT, Ballabh P, Valcarcel-Ares MN, Farley J, Koller A, Henthorn JC, Bass C, Sonntag WE, Ungvari Z, Csiszar A (2012) Liver-specific knockdown of IGF-1 decreases vascular oxidative stress resistance by impairing the Nrf2-dependent antioxidant response: a novel model of vascular aging. J Gerontol A Biol Sci Med Sci 67:313–329. https://doi.org/10.1093/gerona/glr164
Bake S, Okoreeh AK, Alaniz RC, Sohrabji F (2016) Insulin-Like Growth Factor (IGF)-I Modulates Endothelial Blood-Brain Barrier Function in Ischemic Middle-Aged Female Rats. Endocrinology 157:61–69. https://doi.org/10.1210/en.2015-1840
Banjara M, Ghosh C (2017) Sterile Neuroinflammation and Strategies for Therapeutic Intervention. Int J Inflam 2017:8385961. https://doi.org/10.1155/2017/8385961
Belity T, Hoffman JR, Horowitz M, Epstein Y, Bruchim Y, Cohen H (2022) beta-Alanine Supplementation Attenuates the Neurophysiological Response in Animals Exposed to an Acute Heat Stress. J Diet Suppl 19:443–458. https://doi.org/10.1080/19390211.2021.1889734
Bellini MJ, Hereñú CB, Goya RG, Garcia-Segura LM (2011) Insulin-like growth factor-I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide. J Neuroinflammation 8:21. https://doi.org/10.1186/1742-2094-8-21
Bianchi VE, Locatelli V, Rizzi L (2017) Neurotrophic and Neuroregenerative Effects of GH/IGF1. Int J Mol Sci 18. https://doi.org/10.3390/ijms18112441
Bin-Jumah M, Abd El-Hack ME, Abdelnour SA, Hendy YA, Ghanem HA, Alsafy SA, Khafaga AF, Noreldin AE, Shaheen H, Samak D, Momenah MA, Allam AA, AlKahtane AA, Alkahtani S, Abdel-Daim MM, Aleya L (2020) Potential use of chromium to combat thermal stress in animals: A review. Sci Total Environ 707:135996. https://doi.org/10.1016/j.scitotenv.2019.135996
Bompadre TFV, Moretti DB, Sakita GZ, Ieda EH, Martinez MIV, Fernandes EAN, Machado-Neto R, Abdalla AL, Louvandini H (2020) Long-term chromium picolinate supplementation improves colostrum profile of Santa Ines ewe. Biol Trace Elem Res 193:414–421. https://doi.org/10.1007/s12011-019-01741-3
Bouchama A, Knochel JP (2002) Heat stroke. N Engl J Med 346:1978–1988. https://doi.org/10.1056/NEJMra011089
Carro E, Torres-Aleman I (2006) Serum insulin-like growth factor I in brain function. Keio J Med 55:59–63. https://doi.org/10.2302/kjm.55.59
Chandrika BB, Yang C, Ou Y, Feng X, Muhoza D, Holmes AF, Theus S, Deshmukh S, Haun RS, Kaushal GP (2015) Endoplasmic Reticulum Stress-Induced Autophagy Provides Cytoprotection from Chemical Hypoxia and Oxidant Injury and Ameliorates Renal Ischemia-Reperfusion Injury. PLoS One 10:e0140025. https://doi.org/10.1371/journal.pone.0140025
Chauhan NR, Kapoor M, Prabha Singh L, Gupta RK, Chand Meena R, Tulsawani R, Nanda S, Bala Singh S (2017) Heat stress-induced neuroinflammation and aberration in monoamine levels in hypothalamus are associated with temperature dysregulation. Neuroscience 358:79–92. https://doi.org/10.1016/j.neuroscience.2017.06.023
Chauhan SS, Rashamol VP, Bagath M, Sejian V, Dunshea FR (2021) Impacts of heat stress on immune responses and oxidative stress in farm animals and nutritional strategies for amelioration. Int J Biometeorol 65:1231–1244. https://doi.org/10.1007/s00484-021-02083-3
Chen F, Wang CC, Kim E, Harrison LE (2008) Hyperthermia in combination with oxidative stress induces autophagic cell death in HT-29 colon cancer cells. Cell Biol Int 32:715–723. https://doi.org/10.1016/j.cellbi.2008.02.010
Chen YL, Lin JD, Hsia TL, Mao FC, Hsu CH, Pei D (2014) The effect of chromium on inflammatory markers, 1st and 2nd phase insulin secretion in type 2 diabetes. Eur J Nutr 53:127–133. https://doi.org/10.1007/s00394-013-0508-8
Chen WY, Mao FC, Liu CH, Kuan YH, Lai NW, Wu CC, Chen CJ (2016) Chromium supplementation improved post-stroke brain infarction and hyperglycemia. Metab Brain Dis 31:289–297. https://doi.org/10.1007/s11011-015-9749-y
Chen S, Yong Y, Ju X (2021) Effect of heat stress on growth and production performance of livestock and poultry: Mechanism to prevention. J Therm Biol 99:103019. https://doi.org/10.1016/j.jtherbio.2021.103019
Chen XL, Zeng YB, Liu LX, Song QL, Zou ZH, Wei QP, Song WJ (2021) Effects of dietary chromium propionate on laying performance, egg quality, serum biochemical parameters and antioxidant status of laying ducks under heat stress. Animal 15:100081. https://doi.org/10.1016/j.animal.2020.100081
Cheng RY, Alvord WG, Powell D, Kasprzak KS, Anderson LM (2002) Increased serum corticosterone and glucose in offspring of chromium(III)-treated male mice. Environ Health Perspect 110:801–804. https://doi.org/10.1289/ehp.02110801
Chowdhury VS, Tomonaga S, Ikegami T, Erwan E, Ito K, Cockrem JF, Furuse M (2014) Oxidative damage and brain concentrations of free amino acid in chicks exposed to high ambient temperature. Comp Biochem Physiol A Mol Integr Physiol 169:70–76. https://doi.org/10.1016/j.cbpa.2013.12.020
De Geyter D, De Smedt A, Stoop W, De Keyser J, Kooijman R (2016) Central IGF-I Receptors in the Brain are Instrumental to Neuroprotection by Systemically Injected IGF-I in a Rat Model for Ischemic Stroke. CNS Neurosci Ther 22:611–616. https://doi.org/10.1111/cns.12550
Di Patria L, Annibalini G, Morrone A, Ferri L, Saltarelli R, Galluzzi L, Diotallevi A, Bocconcelli M, Donati MA, Barone R, Guerrini R, Jaeken J, Stocchi V, Barbieri E (2022) Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation. Cell Mol Life Sci 79:150. https://doi.org/10.1007/s00018-022-04180-x
Ding H, Jiang Y, Jiang Y, Yuan D, Xiao L (2020) Ulinastatin attenuates monocyte-endothelial adhesion via inhibiting ROS transfer between the neighboring vascular endothelial cells mediated by Cx43. Am J Transl Res 12:4326–4336
Dong Z, Zhou J, Zhang Y, Chen Y, Yang Z, Huang G, Chen Y, Yuan Z, Peng Y, Cao T (2017) Astragaloside-IV Alleviates Heat-Induced Inflammation by Inhibiting Endoplasmic Reticulum Stress and Autophagy. Cell Physiol Biochem 42:824–837. https://doi.org/10.1159/000478626
Dukay B, Csoboz B, Toth ME (2019) Heat-Shock Proteins in Neuroinflammation. Front Pharmacol 10:920. https://doi.org/10.3389/fphar.2019.00920
Dyer AH, Vahdatpour C, Sanfeliu A, Tropea D (2016) The role of Insulin-Like Growth Factor 1 (IGF-1) in brain development, maturation and neuroplasticity. Neuroscience 325:89–99. https://doi.org/10.1016/j.neuroscience.2016.03.056
Ebi KL, Capon A, Berry P, Broderick C, de Dear R, Havenith G, Honda Y, Kovats RS, Ma W, Malik A, Morris NB, Nybo L, Seneviratne SI, Vanos J, Jay O (2021) Hot weather and heat extremes: health risks. Lancet 398:698–708. https://doi.org/10.1016/s0140-6736(21)01208-3
Eckert D, Rapp F, Tsedeke AT, Molendowska J, Lehn R, Langhans M, Fournier C, Rödel F, Hehlgans S (2021) ROS- and Radiation Source-Dependent Modulation of Leukocyte Adhesion to Primary Microvascular Endothelial Cells. Cells 11. https://doi.org/10.3390/cells11010072
Estes ML, McAllister AK (2014) Alterations in immune cells and mediators in the brain: it’s not always neuroinflammation! Brain Pathol 24:623–630. https://doi.org/10.1111/bpa.12198
Falomir-Lockhart E, Dolcetti FJC, García-Segura LM, Hereñú CB, Bellini MJ (2019) IGF1 Gene Therapy Modifies Microglia in the Striatum of Senile Rats. Front Aging Neurosci 11:48. https://doi.org/10.3389/fnagi.2019.00048
Falomir-Lockhart E, Dolcetti FJC, Herrera ML, Pennini J, Zappa Villar MF, Salinas G, Portiansky E, Spittau B, Lacunza E, Hereñú CB, Bellini MJ (2022) IGF-1 Gene Transfer Modifies Inflammatory Environment and Gene Expression in the Caudate-Putamen of Aged Female Rat Brain. Mol Neurobiol 59:3337–3352. https://doi.org/10.1007/s12035-022-02791-w
Fang XS, Zhang MH, Guo JY, Jin Z (2019) Effects of insulin-like growth factor-1 on endoplasmic reticulum stress and autophagy in rat gastric smooth muscle cells cultured at different glucose concentrations in vitro. Mol Cell Biochem 451:11–20. https://doi.org/10.1007/s11010-018-3388-7
Ferger AI, Campanelli L, Reimer V, Muth KN, Merdian I, Ludolph AC, Witting A (2010) Effects of mitochondrial dysfunction on the immunological properties of microglia. J Neuroinflammation 7:45. https://doi.org/10.1186/1742-2094-7-45
Fernandez S, Fernandez AM, Lopez-Lopez C, Torres-Aleman I (2007) Emerging roles of insulin-like growth factor-I in the adult brain. Growth Horm IGF Res 17:89–95. https://doi.org/10.1016/j.ghir.2007.01.006
Giuliano JS Jr, Lahni PM, Wong HR, Wheeler DS (2011) Pediatric Sepsis - Part V: Extracellular Heat Shock Proteins: Alarmins for the Host Immune System. Open Inflamm J 4:49–60. https://doi.org/10.2174/1875041901104010049
Goel A (2021) Heat stress management in poultry. J Anim Physiol Anim Nutr (Berl) 105:1136–1145. https://doi.org/10.1111/jpn.13496
Gong J, Wang XZ, Wang T, Chen JJ, Xie XY, Hu H, Yu F, Liu HL, Jiang XY, Fan HD (2017) Molecular signal networks and regulating mechanisms of the unfolded protein response. J Zhejiang Univ Sci B 18:1–14. https://doi.org/10.1631/jzus.B1600043
Gonzalez-Rivas PA, Chauhan SS, Ha M, Fegan N, Dunshea FR, Warner RD (2020) Effects of heat stress on animal physiology, metabolism, and meat quality: A review. Meat Sci 162:108025. https://doi.org/10.1016/j.meatsci.2019.108025
Guzik TJ, Korbut R, Adamek-Guzik T (2003) Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol 54:469–487
Hammond AC, Elsasser TH, Kunkle WE, Rumsey TS, Williams MJ, Butts WT (1990) Effects of winter nutrition and summer pasture or a feedlot diet on plasma insulin-like growth factor I (IGF-I) and the relationship between circulating concentrations of IGF-I and thyroid hormones in steers. Domest Anim Endocrinol 7:465–475. https://doi.org/10.1016/0739-7240(90)90004-j
Harvey LD, Yin Y, Attarwala IY, Begum G, Deng J, Yan HQ, Dixon CE, Sun D (2015) Administration of DHA Reduces Endoplasmic Reticulum Stress-Associated Inflammation and Alters Microglial or Macrophage Activation in Traumatic Brain Injury. ASN Neuro 7. https://doi.org/10.1177/1759091415618969
Hernandez-Garzón E, Fernandez AM, Perez-Alvarez A, Genis L, Bascuñana P, Fernandez de la Rosa R, Delgado M, Angel Pozo M, Moreno E, McCormick PJ, Santi A, Trueba-Saiz A, Garcia-Caceres C, Tschöp MH, Araque A, Martin ED, Torres Aleman I (2016) The insulin-like growth factor I receptor regulates glucose transport by astrocytes. Glia 64:1962–1971. https://doi.org/10.1002/glia.23035
Herrera ML, Bandin S, Champarini LG, Herenu CB, Bellini MJ (2021) Intramuscular insulin-like growth factor-1 gene therapy modulates reactive microglia after traumatic brain injury. Brain Res Bull 175:196–204. https://doi.org/10.1016/j.brainresbull.2021.07.023
Higashi Y, Sukhanov S, Anwar A, Shai SY, Delafontaine P (2010) IGF-1, oxidative stress and atheroprotection. Trends Endocrinol Metab 21:245–254. https://doi.org/10.1016/j.tem.2009.12.005
Hsuan YC, Lin CH, Chang CP, Lin MT (2016) Mesenchymal stem cell-based treatments for stroke, neural trauma, and heat stroke. Brain Behav 6:e00526. https://doi.org/10.1002/brb3.526
Ivan DC, Berve KC, Walthert S, Monaco G, Borst K, Bouillet E, Ferreira F, Lee H, Steudler J, Buch T, Prinz M, Engelhardt B, Locatelli G (2023) Insulin-like growth factor-1 receptor controls the function of CNS-resident macrophages and their contribution to neuroinflammation. Acta Neuropathol Commun 11:35. https://doi.org/10.1186/s40478-023-01535-8
Ji J, Xue TF, Guo XD, Yang J, Guo RB, Wang J, Huang JY, Zhao XJ, Sun XL (2018) Antagonizing peroxisome proliferator-activated receptor gamma facilitates M1-to-M2 shift of microglia by enhancing autophagy via the LKB1-AMPK signaling pathway. Aging Cell 17:e12774. https://doi.org/10.1111/acel.12774
Jiang CT, Wu WF, Deng YH, Ge JW (2020) Modulators of microglia activation and polarization in ischemic stroke (Review). Mol Med Rep 21:2006–2018. https://doi.org/10.3892/mmr.2020.11003
Jonsson NN, McGowan MR, McGuigan K, Davison TM, Hussain AM, Kafi M, Matschoss A (1997) Relationships among calving season, heat load, energy balance and postpartum ovulation of dairy cows in a subtropical environment. Animal Reproduction Science 47:315–326. https://doi.org/10.1016/S0378-4320(97)00014-6
Jung KA, Kwak MK (2010) The Nrf2 system as a potential target for the development of indirect antioxidants. Molecules 15:7266–7291. https://doi.org/10.3390/molecules15107266
Kagan JC, Medzhitov R (2006) Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling. Cell 125:943–955. https://doi.org/10.1016/j.cell.2006.03.047
Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11:373–384. https://doi.org/10.1038/ni.1863
Kazanis I, Bozas E, Philippidis H, Stylianopoulou F (2003) Neuroprotective effects of insulin-like growth factor-I (IGF-I) following a penetrating brain injury in rats. Brain Res 991:34–45. https://doi.org/10.1016/s0006-8993(03)03525-x
Kellar D, Craft S (2020) Brain insulin resistance in Alzheimer’s disease and related disorders: mechanisms and therapeutic approaches. Lancet Neurol 19:758–766. https://doi.org/10.1016/s1474-4422(20)30231-3
Khodavirdipour A, Haddadi F, Keshavarzi S (2020) Chromium Supplementation; Negotiation with Diabetes Mellitus, Hyperlipidemia and Depression. J Diabetes Metab Disord 19:585–595. https://doi.org/10.1007/s40200-020-00501-8
Kikusato M, Yoshida H, Furukawa K, Toyomizu M (2015) Effect of heat stress-induced production of mitochondrial reactive oxygen species on NADPH oxidase and heme oxygenase-1 mRNA levels in avian muscle cells. J Therm Biol 52:8–13. https://doi.org/10.1016/j.jtherbio.2015.04.005
Kim JY, Yenari MA (2013) The immune modulating properties of the heat shock proteins after brain injury. Anat Cell Biol 46:1–7. https://doi.org/10.5115/acb.2013.46.1.1
Kim Y, Li E, Park S (2012) Insulin-like growth factor-1 inhibits 6-hydroxydopamine-mediated endoplasmic reticulum stress-induced apoptosis via regulation of heme oxygenase-1 and Nrf2 expression in PC12 cells. Int J Neurosci 122:641–649. https://doi.org/10.3109/00207454.2012.702821
Kim YW, West XZ, Byzova TV (2013) Inflammation and oxidative stress in angiogenesis and vascular disease. J Mol Med (Berl) 91:323–328. https://doi.org/10.1007/s00109-013-1007-3
Kim W, Lee W, Huh E, Choi E, Jang YP, Kim YK, Lee TH, Oh MS (2019) Ephedra sinica Stapf and Gypsum Attenuates Heat-Induced Hypothalamic Inflammation in Mice. Toxins (Basel) 12. https://doi.org/10.3390/toxins12010016
Kipp M, Norkute A, Johann S, Lorenz L, Braun A, Hieble A, Gingele S, Pott F, Richter J, Beyer C (2008) Brain-region-specific astroglial responses in vitro after LPS exposure. J Mol Neurosci 35:235–243. https://doi.org/10.1007/s12031-008-9057-7
Kipp M (2020) Oligodendrocyte Physiology and Pathology Function. Cells 9. https://doi.org/10.3390/cells9092078
Krikorian R, Eliassen JC, Boespflug EL, Nash TA, Shidler MD (2010) Improved cognitive-cerebral function in older adults with chromium supplementation. Nutr Neurosci 13:116–122. https://doi.org/10.1179/147683010X12611460764084
Kumar V (2019) Toll-like receptors in the pathogenesis of neuroinflammation. J Neuroimmunol 332:16–30. https://doi.org/10.1016/j.jneuroim.2019.03.012
Kumar M, Kaur H, Deka RS, Mani V, Tyagi AK, Chandra G (2015) Dietary Inorganic Chromium in Summer-Exposed Buffalo Calves (Bubalus bubalis): Effects on Biomarkers of Heat Stress, Immune Status, and Endocrine Variables. Biol Trace Elem Res 167:18–27. https://doi.org/10.1007/s12011-015-0272-0
Labandeira-Garcia JL, Costa-Besada MA, Labandeira CM, Villar-Cheda B, Rodriguez-Perez AI (2017) Insulin-Like Growth Factor-1 and Neuroinflammation. Front Aging Neurosci 9:365. https://doi.org/10.3389/fnagi.2017.00365
Lebovitz HE (2001) Insulin resistance: definition and consequences. Exp Clin Endocrinol Diabetes 109(Suppl 2):S135-148. https://doi.org/10.1055/s-2001-18576
Lee WJ (2011) IGF-I Exerts an Anti-inflammatory Effect on Skeletal Muscle Cells through Down-regulation of TLR4 Signaling. Immune Netw 11:223–226. https://doi.org/10.4110/in.2011.11.4.223
Lee JY, Park J, Kim YH, Kim DH, Kim CG, Koh JY (2000) Induction by synaptic zinc of heat shock protein-70 in hippocampus after kainate seizures. Exp Neurol 161:433–441. https://doi.org/10.1006/exnr.1999.7297
Lee W, Moon M, Kim HG, Lee TH, Oh MS (2015) Heat stress-induced memory impairment is associated with neuroinflammation in mice. J Neuroinflammation 12:102. https://doi.org/10.1186/s12974-015-0324-6
Li J, Zhang XY, Wang B, Zou ZM, Wang PY, Xia JK, Li HF (2015) Diffusion tensor imaging of the cerebellum in patients after heat stroke. Acta Neurol Belg 115:147–150. https://doi.org/10.1007/s13760-014-0343-6
Li K, Li J, Zheng J, Qin S (2019) Reactive Astrocytes in Neurodegenerative Diseases. Aging Dis 10:664–675. https://doi.org/10.14336/ad.2018.0720
Li W, Yang GL, Zhu Q, Zhong XH, Nie YC, Li XH, Wang Y (2019) TLR4 promotes liver inflammation by activating the JNK pathway. Eur Rev Med Pharmacol Sci 23:7655–7662. https://doi.org/10.26355/eurrev_201909_18889
Li GM, Liu LP, Yin B, Liu YY, Dong WW, Gong S, Zhang J, Tan JH (2020) Heat stress decreases egg production of laying hens by inducing apoptosis of follicular cells via activating the FasL/Fas and TNF-α systems. Poult Sci 99:6084–6093. https://doi.org/10.1016/j.psj.2020.07.024
Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, Bennett ML, Münch AE, Chung WS, Peterson TC, Wilton DK, Frouin A, Napier BA, Panicker N, Kumar M, Buckwalter MS, Rowitch DH, Dawson VL, Dawson TM, Stevens B, Barres BA (2017) Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541:481–487. https://doi.org/10.1038/nature21029
Lima RS, Risolia PHB, Ispada J, Assumpção M, Visintin JA, Orlandi C, Paula-Lopes FF (2017) Role of insulin-like growth factor 1 on cross-bred Bos indicus cattle germinal vesicle oocytes exposed to heat shock. Reprod Fertil Dev 29:1405–1414. https://doi.org/10.1071/rd15514
Lindhout IA, Murray TE, Richards CM, Klegeris A (2021) Potential neurotoxic activity of diverse molecules released by microglia. Neurochem Int 148:105117. https://doi.org/10.1016/j.neuint.2021.105117
Ling EA, Wong WC (1993) The origin and nature of ramified and amoeboid microglia: a historical review and current concepts. Glia 7:9–18. https://doi.org/10.1002/glia.440070105
Liu F, Cottrell JJ, Furness JB, Rivera LR, Kelly FW, Wijesiriwardana U, Pustovit RV, Fothergill LJ, Bravo DM, Celi P, Leury BJ, Gabler NK, Dunshea FR (2016) Selenium and vitamin E together improve intestinal epithelial barrier function and alleviate oxidative stress in heat-stressed pigs. Exp Physiol 101:801–810. https://doi.org/10.1113/EP085746
Logan S, Pharaoh GA, Marlin MC, Masser DR, Matsuzaki S, Wronowski B, Yeganeh A, Parks EE, Premkumar P, Farley JA, Owen DB, Humphries KM, Kinter M, Freeman WM, Szweda LI, Van Remmen H, Sonntag WE (2018) Insulin-like growth factor receptor signaling regulates working memory, mitochondrial metabolism, and amyloid-β uptake in astrocytes. Mol Metab 9:141–155. https://doi.org/10.1016/j.molmet.2018.01.013
Luo D, Guo Y, Cheng Y, Zhao J, Wang Y, Rong J (2017) Natural product celastrol suppressed macrophage M1 polarization against inflammation in diet-induced obese mice via regulating Nrf2/HO-1, MAP kinase and NF-κB pathways. Aging (Albany NY) 9:2069–2082. https://doi.org/10.18632/aging.101302
Lv J, Li Y, Shi S, Xu X, Wu H, Zhang B, Song Q (2022) Skeletal muscle mitochondrial remodeling in heart failure: An update on mechanisms and therapeutic opportunities. Biomed Pharmacother 155:113833. https://doi.org/10.1016/j.biopha.2022.113833
Lyman M, Lloyd DG, Ji X, Vizcaychipi MP, Ma D (2014) Neuroinflammation: the role and consequences. Neurosci Res 79:1–12. https://doi.org/10.1016/j.neures.2013.10.004
Ma Q, Battelli L, Hubbs AF (2006) Multiorgan autoimmune inflammation, enhanced lymphoproliferation, and impaired homeostasis of reactive oxygen species in mice lacking the antioxidant-activated transcription factor Nrf2. Am J Pathol 168:1960–1974. https://doi.org/10.2353/ajpath.2006.051113
Ma Z, Lu Y, Yang F, Li S, He X, Gao Y, Zhang G, Ren E, Wang Y, Kang X (2020) Rosmarinic acid exerts a neuroprotective effect on spinal cord injury by suppressing oxidative stress and inflammation via modulating the Nrf2/HO-1 and TLR4/NF-κB pathways. Toxicol Appl Pharmacol 397:115014. https://doi.org/10.1016/j.taap.2020.115014
Mahran YF (2020) New insights into the protection of growth hormone in cisplatin-induced nephrotoxicity: The impact of IGF-1 on the Keap1-Nrf2/HO-1 signaling. Life Sci 253:117581. https://doi.org/10.1016/j.lfs.2020.117581
Maret W (2019) Chromium Supplementation in Human Health, Metabolic Syndrome, and Diabetes. Met Ions Life Sci 19. https://doi.org/10.1515/9783110527872-015
Marwarha G, Claycombe K, Schommer J, Collins D, Ghribi O (2016) Palmitate-induced Endoplasmic Reticulum stress and subsequent C/EBPalpha Homologous Protein activation attenuates leptin and Insulin-like growth factor 1 expression in the brain. Cell Signal 28:1789–1805. https://doi.org/10.1016/j.cellsig.2016.08.012
Meares GP, Liu Y, Rajbhandari R, Qin H, Nozell SE, Mobley JA, Corbett JA, Benveniste EN (2014) PERK-dependent activation of JAK1 and STAT3 contributes to endoplasmic reticulum stress-induced inflammation. Mol Cell Biol 34:3911–3925. https://doi.org/10.1128/mcb.00980-14
Medzhitov R (2008) Origin and physiological roles of inflammation. Nature 454:428–435. https://doi.org/10.1038/nature07201
Miltiadous P, Stamatakis A, Stylianopoulou F (2010) Neuroprotective effects of IGF-I following kainic acid-induced hippocampal degeneration in the rat. Cell Mol Neurobiol 30:347–360. https://doi.org/10.1007/s10571-009-9457-4
Miltiadous P, Stamatakis A, Koutsoudaki PN, Tiniakos DG, Stylianopoulou F (2011) IGF-I ameliorates hippocampal neurodegeneration and protects against cognitive deficits in an animal model of temporal lobe epilepsy. Exp Neurol 231:223–235. https://doi.org/10.1016/j.expneurol.2011.06.014
Młyniec K, Davies CL, de Agüero Sánchez IG, Pytka K, Budziszewska B, Nowak G (2014) Essential elements in depression and anxiety Part I. Pharmacol Rep 66:534–544. https://doi.org/10.1016/j.pharep.2014.03.001
Moon EJ, Sonveaux P, Porporato PE, Danhier P, Gallez B, Batinic-Haberle I, Nien YC, Schroeder T, Dewhirst MW (2010) NADPH oxidase-mediated reactive oxygen species production activates hypoxia-inducible factor-1 (HIF-1) via the ERK pathway after hyperthermia treatment. Proc Natl Acad Sci U S A 107:20477–20482. https://doi.org/10.1073/pnas.1006646107
Moon M, Huh E, Lee W, Song EJ, Hwang DS, Lee TH, Oh MS (2017) Coptidis Rhizoma Prevents Heat Stress-Induced Brain Damage and Cognitive Impairment in Mice. Nutrients 9. https://doi.org/10.3390/nu9101057
Morrell JM (2020) Heat stress and bull fertility. Theriogenology 153:62–67. https://doi.org/10.1016/j.theriogenology.2020.05.014
Morvaridzadeh M, Estevao MD, Qorbani M, Heydari H, Hosseini AS, Fazelian S, Belancic A, Persad E, Rezamand G, Heshmati J (2022) The effect of chromium intake on oxidative stress parameters: A systematic review and meta-analysis. J Trace Elem Med Biol 69:126879. https://doi.org/10.1016/j.jtemb.2021.126879
Munoz K, Wasnik S, Abdipour A, Bi H, Wilson SM, Tang X, Ghahramanpouri M, Baylink DJ (2021) The Effects of Insulin-Like Growth Factor I and BTP-2 on Acute Lung Injury. Int J Mol Sci 22. https://doi.org/10.3390/ijms22105244
Nakabeppu Y (2019) Origins of Brain Insulin and Its Function. Adv Exp Med Biol 1128:1–11. https://doi.org/10.1007/978-981-13-3540-2_1
Nasrolahi A, Hosseini L, Farokhi-Sisakht F, Mahmoudi J, Karimi P, Badalzadeh R, Erfani M (2020) Cardioprotective effect of Rosa canina L. methanolic extract on heat shock induced cardiomyocyte injury: An experimental study. J Cardiovasc Thorac Res 12:286–293. https://doi.org/10.34172/jcvtr.2020.47
Nayak D, Roth TL, McGavern DB (2014) Microglia development and function. Annu Rev Immunol 32:367–402. https://doi.org/10.1146/annurev-immunol-032713-120240
Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:1314–1318. https://doi.org/10.1126/science.1110647
Niranjan R (2018) Recent advances in the mechanisms of neuroinflammation and their roles in neurodegeneration. Neurochem Int 120:13–20. https://doi.org/10.1016/j.neuint.2018.07.003
Niu X, Zhao Y, Yang N, Zhao X, Zhang W, Bai X, Li A, Yang W, Lu L (2020) Proteasome activation by insulin-like growth factor-1/nuclear factor erythroid 2-related factor 2 signaling promotes exercise-induced neurogenesis. Stem Cells 38:246–260. https://doi.org/10.1002/stem.3102
Nybo L (2007) Exercise and heat stress: cerebral challenges and consequences. Prog Brain Res 162:29–43. https://doi.org/10.1016/s0079-6123(06)62003-7
Oakes SA, Papa FR (2015) The role of endoplasmic reticulum stress in human pathology. Annu Rev Pathol 10:173–194. https://doi.org/10.1146/annurev-pathol-012513-104649
Obradovic M, Zafirovic S, Soskic S, Stanimirovic J, Trpkovic A, Jevremovic D, Isenovic ER (2019) Effects of IGF-1 on the Cardiovascular System. Curr Pharm Des 25:3715–3725. https://doi.org/10.2174/1381612825666191106091507
Oghbaei H, Hosseini L, Farajdokht F, Rahigh Aghsan S, Majdi A, Sadigh-Eteghad S, Sandoghchian Shotorbani S, Mahmoudi J (2021) Heat stress aggravates oxidative stress, apoptosis, and endoplasmic reticulum stress in the cerebellum of male C57 mice. Mol Biol Rep 48:5881–5887. https://doi.org/10.1007/s11033-021-06582-9
Okoreeh AK, Bake S, Sohrabji F (2017) Astrocyte-specific insulin-like growth factor-1 gene transfer in aging female rats improves stroke outcomes. Glia 65:1043–1058. https://doi.org/10.1002/glia.23142
Orhan C, Sahin N, Tuzcu Z, Komorowski JR, Sahin K (2017) Combined oral supplementation of chromium picolinate, docosahexaenoic acid, and boron enhances neuroprotection in rats fed a high-fat diet. Turk J Med Sci 47:1616–1625. https://doi.org/10.3906/sag-1701-54
Orihuela R, McPherson CA, Harry GJ (2016) Microglial M1/M2 polarization and metabolic states. Br J Pharmacol 173:649–665. https://doi.org/10.1111/bph.13139
Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, Giustetto M, Ferreira TA, Guiducci E, Dumas L, Ragozzino D, Gross CT (2011) Synaptic pruning by microglia is necessary for normal brain development. Science 333:1456–1458. https://doi.org/10.1126/science.1202529
Pardo J, Uriarte M, Cónsole GM, Reggiani PC, Outeiro TF, Morel GR, Goya RG (2016) Insulin-like growth factor-I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats. Eur J Neurosci 44:2120–2128. https://doi.org/10.1111/ejn.13278
Park SE, Dantzer R, Kelley KW, McCusker RH (2011) Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice. J Neuroinflammation 8:12. https://doi.org/10.1186/1742-2094-8-12
Park SE, Lawson M, Dantzer R, Kelley KW, McCusker RH (2011) Insulin-like growth factor-I peptides act centrally to decrease depression-like behavior of mice treated intraperitoneally with lipopolysaccharide. J Neuroinflammation 8:179. https://doi.org/10.1186/1742-2094-8-179
Pavlik A, Aneja IS, Lexa J, Al-Zoabi BA (2003) Identification of cerebral neurons and glial cell types inducing heat shock protein Hsp70 following heat stress in the rat. Brain Res 973:179–189. https://doi.org/10.1016/s0006-8993(03)02476-4
Peng Z, Qiao W, Wang Z, Dai Q, He J, Guo C, Xu J, Zhou A (2010) Chromium improves protein deposition through regulating the mRNA levels of IGF-1, IGF-1R, and Ub in rat skeletal muscle cells. Biol Trace Elem Res 137:226–234. https://doi.org/10.1007/s12011-009-8579-3
Pinto-Benito D, Paradela-Leal C, Ganchala D, de Castro-Molina P, Arevalo MA (2022) IGF-1 regulates astrocytic phagocytosis and inflammation through the p110alpha isoform of PI3K in a sex-specific manner. Glia 70:1153–1169. https://doi.org/10.1002/glia.24163
Piray AH, Foroutanifar S (2021) Effect of Chromium Supplementation on Performance, Carcass Characteristics, Blood Biochemistry, and Immune Response of Unstressed Broiler Chickens: a Dose-Response Meta-Analysis. Biol Trace Elem Res 199:4713–4720. https://doi.org/10.1007/s12011-021-02589-2
Popa-Wagner A, Mitran S, Sivanesan S, Chang E, Buga AM (2013) ROS and brain diseases: the good, the bad, and the ugly. Oxid Med Cell Longev 2013:963520. https://doi.org/10.1155/2013/963520
Puche JE, García-Fernández M, Muntané J, Rioja J, González-Barón S, Castilla Cortazar I (2008) Low doses of insulin-like growth factor-I induce mitochondrial protection in aging rats. Endocrinology 149:2620–2627. https://doi.org/10.1210/en.2007-1563
Rabinovsky ED (2004) The multifunctional role of IGF-1 in peripheral nerve regeneration. Neurol Res 26:204–210. https://doi.org/10.1179/016164104225013851
Ransom B, Behar T, Nedergaard M (2003) New roles for astrocytes (stars at last). Trends Neurosci 26:520–522. https://doi.org/10.1016/j.tins.2003.08.006
Rodrigues TA, Ispada J, Risolia PH, Rodrigues MT, Lima RS, Assumpção ME, Visintin JA, Paula-Lopes FF (2016) Theriogenology 86:2028–2039. https://doi.org/10.1016/j.theriogenology.2016.06.023
Roenfeldt S (1998) You can't afford to ignore heat stress. Dairy Herd Management 35. https://www.proquest.com/tradejournals/you-cant-afford-ignore-heat-stress/docview/215216430/se-2?accountid=28144
Sadaba MC, Martin-Estal I, Puche JE, Castilla-Cortazar I (2016) Insulin-like growth factor 1 (IGF-1) therapy: Mitochondrial dysfunction and diseases. Biochim Biophys Acta 1862:1267–1278. https://doi.org/10.1016/j.bbadis.2016.03.010
Sahin N, Akdemir F, Tuzcu M, Hayirli A, Smith MO, Sahin K (2010) Effects of supplemental chromium sources and levels on performance, lipid peroxidation and proinflammatory markers in heat-stressed quails. Animal Feed Sci Technol 159:143–149. https://doi.org/10.1016/j.anifeedsci.2010.06.004
Sahin K, Tuzcu M, Orhan C, Gencoglu H, Ulas M, Atalay M, Sahin N, Hayirli A, Komorowski JR (2012) The effects of chromium picolinate and chromium histidinate administration on NF-κB and Nrf2/HO-1 pathway in the brain of diabetic rats. Biol Trace Elem Res 150:291–296. https://doi.org/10.1007/s12011-012-9475-9
Sahin K, Tuzcu M, Orhan C, Ali S, Sahin N, Gencoglu H, Ozkan Y, Hayirli A, Gozel N, Komorowski JR (2013) Chromium modulates expressions of neuronal plasticity markers and glial fibrillary acidic proteins in hypoglycemia-induced brain injury. Life Sci 93:1039–1048. https://doi.org/10.1016/j.lfs.2013.10.009
Sahin N, Hayirli A, Orhan C, Tuzcu M, Akdemir F, Komorowski JR, Sahin K (2017) Effects of the supplemental chromium form on performance and oxidative stress in broilers exposed to heat stress. Poult Sci 96:4317–4324. https://doi.org/10.3382/ps/pex249
Schell M, Wardelmann K, Kleinridders A (2021) Untangling the effect of insulin action on brain mitochondria and metabolism. J Neuroendocrinol 33:e12932. https://doi.org/10.1111/jne.12932
Sędzikowska A, Szablewski L (2021) Insulin and Insulin Resistance in Alzheimer's Disease. Int J Mol Sci 22. https://doi.org/10.3390/ijms22189987
Sharma HS, Zimmer C, Westman J, Cervós-Navarro J (1992) Acute systemic heat stress increases glial fibrillary acidic protein immunoreactivity in brain: experimental observations in conscious normotensive young rats. Neuroscience 48:889–901. https://doi.org/10.1016/0306-4522(92)90277-9
Sharma HS, Westman J, Nyberg F (1998) Pathophysiology of brain edema and cell changes following hyperthermic brain injury. Prog Brain Res 115:351–412. https://doi.org/10.1016/s0079-6123(08)62043-9
Shehab-El-Deen MA, Leroy JL, Fadel MS, Saleh SY, Maes D, Van Soom A (2010) Biochemical changes in the follicular fluid of the dominant follicle of high producing dairy cows exposed to heat stress early post-partum. Anim Reprod Sci 117:189–200. https://doi.org/10.1016/j.anireprosci.2009.04.013
Siddiqui K, Bawazeer N, Joy SS (2014) Variation in macro and trace elements in progression of type 2 diabetes. ScientificWorldJournal 2014:461591. https://doi.org/10.1155/2014/461591
Singh P, Chowdhuri DK (2017) Environmental Presence of Hexavalent but Not Trivalent Chromium Causes Neurotoxicity in Exposed Drosophila melanogaster. Mol Neurobiol 54:3368–3387. https://doi.org/10.1007/s12035-016-9909-z
Sofroniew MV (2009) Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci 32:638–647. https://doi.org/10.1016/j.tins.2009.08.002
Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119:7–35. https://doi.org/10.1007/s00401-009-0619-8
Song Y, Pimentel C, Walters K, Boller L, Ghiasvand S, Liu J, Staley KJ, Berdichevsky Y (2016) Neuroprotective levels of IGF-1 exacerbate epileptogenesis after brain injury. Sci Rep 6:32095. https://doi.org/10.1038/srep32095
Spicer MT, Stoecker BJ, Chen T, Spicer LJ (1998) Maternal and fetal insulin-like growth factor system and embryonic survival during pregnancy in rats: interaction between dietary chromium and diabetes. J Nutr 128:2341–2347. https://doi.org/10.1093/jn/128.12.2341
Spielman LJ, Little JP, Klegeris A (2014) Inflammation and insulin/IGF-1 resistance as the possible link between obesity and neurodegeneration. J Neuroimmunol 273:8–21. https://doi.org/10.1016/j.jneuroim.2014.06.004
Sprenkle NT, Sims SG, Sanchez CL, Meares GP (2017) Endoplasmic reticulum stress and inflammation in the central nervous system. Mol Neurodegener 12:42. https://doi.org/10.1186/s13024-017-0183-y
Sui G, Yang C, Wang L, Xiong X, Guo M, Chen Z, Wang F (2021) Exogenous IGF-1 improves tau pathology and neuronal pyroptosis in high-fat diet mice with cognitive dysfunction. Metab Brain Dis 36:2079–2088. https://doi.org/10.1007/s11011-021-00787-4
Sukhanov S, Higashi Y, Shai SY, Vaughn C, Mohler J, Li Y, Song YH, Titterington J, Delafontaine P (2007) IGF-1 reduces inflammatory responses, suppresses oxidative stress, and decreases atherosclerosis progression in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 27:2684–2690. https://doi.org/10.1161/atvbaha.107.156257
Sun Z, Wu K, Gu L, Huang L, Zhuge Q, Yang S, Wang Z (2020) IGF-1R stimulation alters microglial polarization via TLR4/NF-kappaB pathway after cerebral hemorrhage in mice. Brain Res Bull 164:221–234. https://doi.org/10.1016/j.brainresbull.2020.08.026
Tao S, Orellana Rivas RM, Marins TN, Chen YC, Gao J, Bernard JK (2020) Impact of heat stress on lactational performance of dairy cows. Theriogenology 150:437–444. https://doi.org/10.1016/j.theriogenology.2020.02.048
Taylor AR, Robinson MB, Gifondorwa DJ, Tytell M, Milligan CE (2007) Regulation of heat shock protein 70 release in astrocytes: role of signaling kinases. Dev Neurobiol 67:1815–1829. https://doi.org/10.1002/dneu.20559
Tian H, Guo X, Wang X, He Z, Sun R, Ge S, Zhang Z (2013) Chromium picolinate supplementation for overweight or obese adults. Cochrane Database Syst Rev 2013:Cd0100063. https://doi.org/10.1002/14651858.CD010063.pub2
Tian YY, Zhang LY, Dong B, Cao J, Xue JX, Gong LM (2014) Effects of chromium methionine supplementation on growth performance, serum metabolites, endocrine parameters, antioxidant status, and immune traits in growing pigs. Biol Trace Elem Res 162:134–141. https://doi.org/10.1007/s12011-014-0147-9
Tian F, Liu GR, Li N, Yuan G (2017) Insulin-like growth factor I reduces the occurrence of necrotizing enterocolitis by reducing inflammatory response and protecting intestinal mucosal barrier in neonatal rats model. Eur Rev Med Pharmacol Sci 21:4711–4719
Tien L-T, Lee Y-J, Pang Y, Lu S, Lee JW, Tseng C-H, Bhatt AJ, Savich RD, Fan L-W (2017) Neuroprotective Effects of Intranasal IGF-1 against Neonatal Lipopolysaccharide-Induced Neurobehavioral Deficits and Neuronal Inflammation in the Substantia Nigra and Locus Coeruleus of Juvenile Rats. Dev Neurosci 39:443–459. https://doi.org/10.1159/000477898
Ullah Khan R, Naz S, Dhama K (2014) Chromium: Pharmacological Applications in Heat-Stressed Poultry. Int J Pharmacol 10:213–217. https://doi.org/10.3923/ijp.2014.213.217
Urban MJ, Dobrowsky RT, Blagg BS (2012) Heat shock response and insulin-associated neurodegeneration. Trends Pharmacol Sci 33:129–137. https://doi.org/10.1016/j.tips.2011.11.001
Vargas N, Marino F (2016) Heat stress, gastrointestinal permeability and interleukin-6 signaling - Implications for exercise performance and fatigue. Temperature (Austin) 3:240–251. https://doi.org/10.1080/23328940.2016.1179380
Varin A, Gordon S (2009) Alternative activation of macrophages: immune function and cellular biology. Immunobiology 214:630–641. https://doi.org/10.1016/j.imbio.2008.11.009
Vezzani A, Ruegg S (2011) The pivotal role of immunity and inflammatory processes in epilepsy is increasingly recognized: introduction. Epilepsia 52(Suppl 3):1–4. https://doi.org/10.1111/j.1528-1167.2011.03028.x
Vincent JB (2014) Is chromium pharmacologically relevant? J Trace Elem Med Biol 28:397–405. https://doi.org/10.1016/j.jtemb.2014.06.020
Vincent JB (2015) Is the Pharmacological Mode of Action of Chromium(III) as a Second Messenger? Biol Trace Element Res 166:7–12. https://doi.org/10.1007/s12011-015-0231-9
Vincent JB (2017) New Evidence against Chromium as an Essential Trace Element. J Nutr 147:2212–2219. https://doi.org/10.3945/jn.117.255901
Vincent JB (2001) The bioinorganic chemistry of chromium(III). Polyhedron
Walter EJ, Carraretto M (2016) The neurological and cognitive consequences of hyperthermia. Crit Care 20:199. https://doi.org/10.1186/s13054-016-1376-4
Wang MQ, Xu ZR, Li WF, Jiang ZG (2009) Effect of chromium nanocomposite supplementation on growth hormone pulsatile secretion and mRNA expression in finishing pigs. J Anim Physiol Anim Nutr (Berl) 93:520–525. https://doi.org/10.1111/j.1439-0396.2008.00836.x
Wang X, Son YO, Chang Q, Sun L, Hitron JA, Budhraja A, Zhang Z, Ke Z, Chen F, Luo J, Shi X (2011) NADPH oxidase activation is required in reactive oxygen species generation and cell transformation induced by hexavalent chromium. Toxicol Sci 123:399–410. https://doi.org/10.1093/toxsci/kfr180
Wang MQ, Wang C, Du YJ, Li H, Tao WJ, Ye SS, He YD, Chen SY (2014) Effects of chromium-loaded chitosan nanoparticles on growth, carcass characteristics, pork quality, and lipid metabolism in finishing pigs. Livestock Science 161:123–129. https://doi.org/10.1016/j.livsci.2013.12.029
Wang Z, Xiong L, Wang G, Wan W, Zhong C, Zu H (2017) Insulin-like growth factor-1 protects SH-SY5Y cells against beta-amyloid-induced apoptosis via the PI3K/Akt-Nrf2 pathway. Exp Gerontol 87:23–32. https://doi.org/10.1016/j.exger.2016.11.009
Wang Y, Li C, Pan C, Liu E, Zhao X, Ling Q (2019) Alterations to transcriptomic profile, histopathology, and oxidative stress in liver of pikeperch (Sander lucioperca) under heat stress. Fish Shellfish Immunol 95:659–669. https://doi.org/10.1016/j.fsi.2019.11.014
Weninger J, Meseke M, Rana S, Forster E (2021) Heat-Shock Induces Granule Cell Dispersion and Microgliosis in Hippocampal Slice Cultures. Front Cell Dev Biol 9:626704. https://doi.org/10.3389/fcell.2021.626704
White MG, Saleh O, Nonner D, Barrett EF, Moraes CT, Barrett JN (2012) Mitochondrial dysfunction induced by heat stress in cultured rat CNS neurons. J Neurophysiol 108:2203–2214. https://doi.org/10.1152/jn.00638.2011
Wo Y, Ma F, Shan Q, Gao D, Jin Y, Sun P (2023) Plasma metabolic profiling reveals that chromium yeast alleviates the negative effects of heat stress in mid-lactation dairy cows. Anim Nutr 13:401–410. https://doi.org/10.1016/j.aninu.2023.01.012
Xia W, Wang Y, Zhang Y, Ge X, Lv P, Cheng J, Wei J (2020) Endoplasmic reticulum stress induces growth retardation by inhibiting growth hormone IGF-I axis. Growth Horm IGF Res 55:101341. https://doi.org/10.1016/j.ghir.2020.101341
Yang L, Li F, Zhang H, Ge W, Mi C, Sun R, Liu C (2009) Astrocyte activation and memory impairment in the repetitive febrile seizures model. Epilepsy Res 86:209–220. https://doi.org/10.1016/j.eplepsyres.2009.07.001
Yang C, Sui G, Li D, Wang L, Zhang S, Lei P, Chen Z, Wang F (2021) Exogenous IGF-1 alleviates depression-like behavior and hippocampal mitochondrial dysfunction in high-fat diet mice. Physiol Behav 229:113236. https://doi.org/10.1016/j.physbeh.2020.113236
Yao X, Liu R, Li X, Li Y, Zhang Z, Huang S, Ge Y, Chen X, Yang X (2021) Zinc, selenium and chromium co-supplementation improves insulin resistance by preventing hepatic endoplasmic reticulum stress in diet-induced gestational diabetes rats. J Nutr Biochem 96:108810. https://doi.org/10.1016/j.jnutbio.2021.108810
Yin Y, Chen C, Chen J, Zhan R, Zhang Q, Xu X, Li D, Li M (2017) Cell surface GRP78 facilitates hepatoma cells proliferation and migration by activating IGF-IR. Cell Signal 35:154–162. https://doi.org/10.1016/j.cellsig.2017.04.003
Yoshida T, Delafontaine P (2020) Mechanisms of IGF-1-Mediated Regulation of Skeletal Muscle Hypertrophy and Atrophy. Cells 9. https://doi.org/10.3390/cells9091970
Zegarra-Valdivia J, Fernandez AM, Martinez-Rachadell L, Herrero-Labrador R, Fernandes J, Torres Aleman I (2022) Insulin and insulin-like growth factor-I receptors in astrocytes exert different effects on behavior and Alzheimer´s-like pathology. F1000 Res 11:663. https://doi.org/10.12688/f1000research.121901.3
Zha L, Zeng J, Sun S, Deng H, Luo H, Li W (2009) Chromium(III) nanoparticles affect hormone and immune responses in heat-stressed rats. Biol Trace Elem Res 129:157–169. https://doi.org/10.1007/s12011-008-8282-9
Zhang XY, Li J (2014) Susceptibility-weighted imaging in heat stroke. PLoS One 9:e105247. https://doi.org/10.1371/journal.pone.0105247
Zhang FJ, Weng XG, Wang JF, Zhou D, Zhang W, Zhai CC, Hou YX, Zhu YH (2014) Effects of temperature-humidity index and chromium supplementation on antioxidant capacity, heat shock protein 72, and cytokine responses of lactating cows. J Anim Sci 92:3026–3034. https://doi.org/10.2527/jas.2013-6932
Zhang C, Lu T, Wang GD, Ma C, Zhou YF (2016) Costunolide, an active sesquiterpene lactone, induced apoptosis via ROS-mediated ER stress and JNK pathway in human U2OS cells. Biomed Pharmacother 80:253–259. https://doi.org/10.1016/j.biopha.2016.03.031
Zhao T, Zhu Y, Yao L, Liu L, Li N (2021) IGF-1 alleviates CCL4-induced hepatic cirrhosis and dysfunction of intestinal barrier through inhibition TLR4/NF-κB signaling mediated by down-regulation HMGB1. Ann Hepatol 26:100560. https://doi.org/10.1016/j.aohep.2021.100560
Zhao Y, Zhuang Y, Shi Y, Xu Z, Zhou C, Guo L, Liu P, Wu C, Hu R, Hu G, Guo X, Xu L (2021) Effects of N-acetyl-l-cysteine on heat stress-induced oxidative stress and inflammation in the hypothalamus of hens. J Therm Biol 98:102927. https://doi.org/10.1016/j.jtherbio.2021.102927
Zheng C, Huang Y, Xiao F, Lin X, Lloyd K (2016) Effects of Supplemental Chromium Source and Concentration on Growth, Carcass Characteristics, and Serum Lipid Parameters of Broilers Reared Under Normal Conditions. Biol Trace Elem Res 169:352–358. https://doi.org/10.1007/s12011-015-0419-z
Zhu X, Huang J, Wu Y, Zhao S, Chai X (2023) Effect of Heat Stress on Hippocampal Neurogenesis: Insights into the Cellular and Molecular Basis of Neuroinflammation-Induced Deficits. Cell Mol Neurobiol 43:1–13. https://doi.org/10.1007/s10571-021-01165-5
Zorina NF II, Avrova IO, Zakharova AO, Shpakov, (2023) Prospects for the Use of Intranasally Administered Insulin and Insulin-Like Growth Factor-1 in Cerebral Ischemia. Biochemistry (Mosc) 88:374–391. https://doi.org/10.1134/s0006297923030070
Zou CG, Cao XZ, Zhao YS, Gao SY, Li SD, Liu XY, Zhang Y, Zhang KQ (2009) The molecular mechanism of endoplasmic reticulum stress-induced apoptosis in PC-12 neuronal cells: the protective effect of insulin-like growth factor I. Endocrinology 150:277–285. https://doi.org/10.1210/en.2008-0794
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This work was financially supported by the National Natural Science Foundation of China (No. 32272967).
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SLW wrote the review, SZ and XZ designed the idea of overall review. KH, SG and YM contributed relevant references. SW and YM draw the figures. All authors read and approved the final manuscript.
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Wang, S., Hou, K., Gui, S. et al. Insulin-like growth factor 1 in heat stress-induced neuroinflammation: novel perspective about the neuroprotective role of chromium. Stress Biology 3, 23 (2023). https://doi.org/10.1007/s44154-023-00105-1
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DOI: https://doi.org/10.1007/s44154-023-00105-1