Skip to main content
SpringerLink
Log in

Repeated social defeat stress exacerbates lipopolysaccharide-induced behavioural deficits in mice: ameliorative role of Chrysophyllum albidum fruit extract through anti-neuroinflammation, antioxidant and neurochemical balance

  • Original Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Development of neuropsychiatric disorder is associated with stress-related increase in pro-inflammatory cytokines. Chrysophyllum albidum fruit is an edible tropical fruit containing vitamins and phenolic compounds, well known for their anti-inflammatory and antioxidant activities. This study was designed to investigate the neuroprotective effect of C. albidum fruit extract (CAFE) on stress and lipopolysaccharide (LPS)-induced behavioral and neurochemical impairments in mice. Male Swiss mice were divided into 6 groups (n = 6). Groups 1–3 were orally treated daily for 14 days with normal saline (0.1 mL/10 g), CAFE (100 mg/kg) and Ferulic acid (FA, 10 mg/kg), and left in home cage as controls. Groups 4–6 were treated similarly but subjected to repeated social defeat (RSD) stress using the resident-intruder model from days 1–14. The RSD-animals were injected with LPS (125 µg/kg, i.p) 60 min after each RSD session from days 8–14. Neurobehavioral functions: locomotor, cognitive and anxiety-like behaviors were assessed 24 h after the last treatment. Pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α), dopamine, acetylcholinesterase, glutamic acid decarboxylase (GAD), malondialdehyde, nitrites, and reduced glutathione (GSH) were determined in brain tissue. CAFE significantly attenuated RSD and LPS-induced hypolocomotion, cognitive impairment and anxiety-like behavior when compared to the control. Treatment with CAFE also significantly reversed the negative effects of RSD and LPS on pro-inflammatory cytokines, dopamine, acetylcholinesterase, GAD, and oxidative-nitrosative stress levels. The findings clearly indicated that Chrysophyllum albidum fruit demonstrated neuroprotective effects and can play a key role in mitigating against chronic stress and inflammation linked to neuropsychiatric disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Data availability

The data set is available with the corresponding author upon request.

Code availability (software application of custom code)

Not applicable.

References

  • Adebiyi OE, Olayemi FO, Olopade JO, Tan NH (2019) Βeta-sitosterol enhances motor coordination, attenuates memory loss and demyelination in a vanadium-induced model of experimental neurotoxicity. Pathophysiology 26(1):21–29

    Article  CAS  PubMed  Google Scholar 

  • Ajayi AM, Umukoro S, Ben-Azu B, Adzu B, Ademowo OG (2017) Toxicity and protective effect of phenolic-enriched ethylacetate fraction of Ocimum gratissimum (Linn.) leaf against acute inflammation and oxidative stress in rats. Drug Dev Res 78(3–4):135–145

    Article  CAS  PubMed  Google Scholar 

  • Ajayi AM, Ben-Azu B, Onasanwo SA, Adeoluwa O, Eduviere A, Ademowo OG (2019) Flavonoid-rich fraction of Ocimum gratissimum attenuates lipopolysaccharide-induced sickness behavior, inflammatory and oxidative stress in mice. Drug Research 69(03):151–158

    Article  CAS  PubMed  Google Scholar 

  • Ajayi AM, Badaki VB, Ariyo OO, Ben-Azu B, Asejeje FO, Adedapo AD (2020a) Chrysophyllum albidum fruit peel attenuates nociceptive pain and inflammatory response in rodents by inhibition of pro-inflammatory cytokines and COX-2 expression through suppression of NF-κB activation. Nutr Res 77:73–84

    Article  CAS  PubMed  Google Scholar 

  • Ajayi AM, Chidebe EO, Ben-Azu B, Umukoro S (2020b) Chrysophyllum albidum (African star apple) fruit-supplemented diet enhances cognitive functions and attenuates lipopolysaccharide-induced memory impairment, oxidative stress, and release of proinflammatory cytokines. Nutrire 45(2):1–13

    Article  Google Scholar 

  • Ajayi AM, Adedapo AD, Badaki VB, Oyagbemi AA, Adedapo AA (2021) Chrysophyllum albidum fruit ethanol extract ameliorates hyperglycaemia and elevated blood pressure in streptozotocin-induced diabetic rats through modulation of oxidative stress, NF-κB and PPAR-γ. Biomed Pharmacother 141:111879

    Article  CAS  PubMed  Google Scholar 

  • Allen J, Balfour R, Bell R, Marmot M (2014) Social determinants of mental health. Int Rev Psychiatry 26(4):392–407

    Article  PubMed  Google Scholar 

  • Atrooz F, Alkadhi KA, Salim S (2021) Understanding stress: Insights from rodent models. Curr Res Neurobiol 2:100013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Audet MC, Jacobson-Pick S, Wann BP, Anisman H (2011) Social defeat promotes specific cytokine variations within the prefrontal cortex upon subsequent aggressive or endotoxin challenges. Brain Behav Immun 25(6):1197–1205

    Article  CAS  PubMed  Google Scholar 

  • Baik JH (2020) Stress and the dopaminergic reward system. Exp Mol Med 52(12):1879–1890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barone E, Calabrese V, Mancuso C (2009) Ferulic acid and its therapeutic potential as a hormetin for age-related diseases. Biogerontology 10(2):97–108

    Article  CAS  PubMed  Google Scholar 

  • Ben-Azu B, Emokpae O, Ajayi AM, Jarikre TA, Orhode V, Aderibigbe AO, Umukoro S, Iwalewa EO (2020) Repeated psychosocial stress causes glutamic acid decarboxylase isoform-67, oxidative-Nox-2 changes and neuroinflammation in mice: prevention by treatment with a neuroactive flavonoid, morin. Brain Res 1744:146917

    Article  CAS  PubMed  Google Scholar 

  • Bergamini G, Mechtersheimer J, Azzinnari D, Sigrist H, Buerge M, Dallmann R, Freije R, Kouraki A, Opacka-Juffy J, Seifritz E, Ferger B, Suter T, Pryce CR (2018) Chronic social stress induces peripheral and central immune activation, blunted mesolimbic dopamine function, and reduced reward-directed behaviour in mice. Neurobiol Stress 8:42–56

    Article  PubMed  PubMed Central  Google Scholar 

  • Berton O, McClung CA, DiLeone RJ, Krishnan V, Renthal W, Russo SJ, Nestler EJ (2006) Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 311:864–868

    Article  CAS  PubMed  Google Scholar 

  • Bourin M (2015) Animal models for screening anxiolytic-like drugs: a perspective. Dialogues Clin Neurosci 17(3):295

    Article  PubMed  PubMed Central  Google Scholar 

  • Buckmaster CA, Eichenbaum H, Amaral DG, Suzuki WA, Rapp PR (2004) Entorhinal cortex lesions disrupt the relational organization of memory in monkeys. J Neurosci 24(44):9811–9825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Casadesus G, Shukitt-Hale B, Stellwagen HM, Zhu X, Lee HG, Smith MA, Joseph JA (2004) Modulation of hippocampal plasticity and cognitive behavior by short-term blueberry supplementation in aged rats. Nutr Neurosci 7(5–6):309–316

    Article  CAS  PubMed  Google Scholar 

  • Choubey P, Kwatra M, Pandey SN, Kumar D, Dwivedi DK, Rajput P, Mishra A, Lahkar M, Jangra A (2019) Ameliorative effect of fisetin against lipopolysaccharide and restraint stress-induced behavioral deficits via modulation of NF-κB and IDO-1. Psychopharmacology 236(2):741–752

    Article  CAS  PubMed  Google Scholar 

  • Dhalaria R, Verma R, Kumar D, Puri S, Tapwal A, Kumar V, Nepovimova E, Kuca K (2020) Bioactive compounds of edible fruits with their anti-aging properties: A comprehensive review to prolong human life. Antioxidants 9(11):1123

    Article  CAS  PubMed Central  Google Scholar 

  • Doostkam A, Bassiri-Jahromi S, Iravani K (2020) Punica granatum with multiple effects in chronic diseases. Int J Fruit Sci 20(3):471–494

    Article  Google Scholar 

  • Eimerbrink MJ (2017) Combined effects of repeated social defeat and inflammation on the accumulation of amyloid-β within the hippocampus. Texas Christian University. (Doctoral Dissertation).

  • Ellman GL, Courtney KD, Andres V Jr, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7(2):88–95

    Article  CAS  PubMed  Google Scholar 

  • Erukainure OL, Salau VF, Xiao X, Matsabisa MG, Koorbanally NA, Islam MS (2021) Bioactive compounds of African star apple (Chrysophyllum albidum G. Don) and its modulatory effect on metabolic activities linked to type 2 diabetes in isolated rat psoas muscle. J Food Biochem 45(1):e13576

    Article  CAS  PubMed  Google Scholar 

  • Esterbauer H, Cheeseman KH (1990) [42] Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 186:407–421

    Article  CAS  PubMed  Google Scholar 

  • Favoretto CA, Nunes YC, Macedo GC, Lopes JSR, Quadros IMH (2020) Chronic social defeat stress: Impacts on ethanol-induced stimulation, corticosterone response, and brain monoamine levels. J Psychopharmacol 34(4):412–419

    Article  CAS  PubMed  Google Scholar 

  • Ferbinteanu J (2016) Contributions of hippocampus and striatum to memory-guided behavior depend on past experience. J Neurosci 36(24):6459–6470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fogaça MV, Duman RS (2019) Cortical GABAergic dysfunction in stress and depression: new insights for therapeutic interventions. Front Cell Neurosci 13:87

    Article  PubMed  PubMed Central  Google Scholar 

  • Frasquilho D, Matos MG, Salonna F, Guerreiro D, Storti CC, Gaspar T, Caldas-de-Almeida JM (2015) Mental health outcomes in times of economic recession: a systematic literature review. BMC Public Health 16(1):115

    Article  Google Scholar 

  • Goulart BK, De Lima MN, De Farias CB, Reolon GK, Almeida VR, Quevedo J, Kapczinski F, Schröder N, Roesler R (2010) Ketamine impairs recognition memory consolidation and prevents learning-induced increase in hippocampal brain-derived neurotrophic factor levels. Neuroscience 167(4):969–973

    Article  CAS  PubMed  Google Scholar 

  • Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 126(1):131–138

    Article  CAS  PubMed  Google Scholar 

  • Huang Y, Su L, Wu J (2016) Pyridoxine supplementation improves the activity of recombinant glutamate decarboxylase and the enzymatic production of gama-aminobutyric acid. PLoS ONE 11(7):e0157466

    Article  PubMed  PubMed Central  Google Scholar 

  • Ibrahim HO, Osilesi O, Adebawo OO, Onajobi FD, Karigidi KO, Muhammad LB (2017) Nutrients compositions and phytochemical contents of edible parts of Chrysophyllum albidum fruit. J Nutr Food Sci 7(2):1–9

    Google Scholar 

  • Idowu TO, Iwalewa EO, Aderogba MA, Akinpelu BA, Ogundaini AO (2006) Antinociceptive, anti-inflammatory and antioxidant activities of eleagnine: An alkaloid isolated from Chrysophyllum albidum seed cotyledons. J Biol Sci 6(6):1029–1034

    Article  CAS  Google Scholar 

  • Iheanyichukwu E, Caleb NJ, Okezie UI, Nkechinyere EA (2017) Nutritional properties and antioxidant activity of Chrysophyllum africanum leaves and pulp. J Mol Pharm Org Process Res 5:139

    Article  Google Scholar 

  • Isingrini E, Perret L, Rainer Q, Sagueby S, Moquin L, Gratton A, Giros B (2016) Selective genetic disruption of dopaminergic, serotonergic and noradrenergic neurotransmission: insights into motor, emotional and addictive behaviour. J Psychiatry Neurosci 41(3):169–181

    Article  PubMed  Google Scholar 

  • Khoo HE, Azlan A, Kong KW, Ismail A (2016) Phytochemicals and medicinal properties of indigenous tropical fruits with potential for commercial development. Evid Based Complement Alternat Med 2016:1–20

    Article  Google Scholar 

  • Kinsey SG, Bailey MT, Sheridan JF, Padgett DA (2008) The inflammatory response to social defeat is increased in older mice. Physiol Behav 93(3):628–636

    Article  CAS  PubMed  Google Scholar 

  • Komysheva NP, Shishkina GT, Kalinina TS, Dygalo NN (2021) Features of the responses of the protective systems of the brain in adult rats to stressors and lipopolysaccharide. Neurosci Behav Physiol 51(3):367–371

    Article  CAS  Google Scholar 

  • Koolhaas JM, De Boer SF, Buwalda B, Meerlo P (2017) Social stress models in rodents: Towards enhanced validity. Neurobiology of Stress 6:104–112

    Article  CAS  PubMed  Google Scholar 

  • Kumar N, Pruthi V (2014) Potential applications of ferulic acid from natural sources. Biotechnol Rep 4:86–93

    Article  CAS  Google Scholar 

  • Laine MA, Sokolowska E, Dudek M, Callan SA, Hyytiä P, Hovatta I (2017) Brain activation induced by chronic psychosocial stress in mice. Sci Rep 7(1):1–11

    Article  CAS  Google Scholar 

  • Lazarov O, Hollands C (2016) Hippocampal neurogenesis: learning to remember. Prog Neurobiol 138:1–18

    Article  PubMed  Google Scholar 

  • Levone BR, Cryan JF, O’Leary OF (2021) Specific sub-regions of the longitudinal axis of the hippocampus mediate behavioural responses to chronic psychosocial stress. Neuropharmacology 201:108843

    Article  CAS  PubMed  Google Scholar 

  • Liu RH (2021) Health-promoting components of fruits and vegetables in the diet. Adv Nutr 4(3):384S-392S

    Article  Google Scholar 

  • Lucassen PJ, Pruessner J, Sousa N, Almeida OF, Van Dam AM, Rajkowska G, Swaab DF, Czéh B (2014) Neuropathology of stress. Acta Neuropathol 127:109–135

    Article  CAS  PubMed  Google Scholar 

  • Martin V, Allaïli N, Euvrard M, Marday T, Riffaud A, Franc B, Lanfumey L (2017) Effect of agomelatine on memory deficits and hippocampal gene expression induced by chronic social defeat stress in mice. Sci Rep 7(1):1–11

    Article  Google Scholar 

  • Neri-Numa IA, Sancho RAS, Pereira APA, Pastore GM (2018) Small Brazilian wild fruits: Nutrients, bioactive compounds, health-promotion properties and commercial interest. Food Res Int 103:345–360

    Article  CAS  PubMed  Google Scholar 

  • Nikolaus S, Wittsack HJ, Beu M, Antke C, De Souza Silva MA, Wickrath F, Muller-Lutz A, Huston JP, Antoch G, Muller H, Hautzel H (2018) GABAergic control of nigrostriatal and mesolimbic dopamine in the rat brain. Front Behav Neurosci 12:38

    Article  PubMed  PubMed Central  Google Scholar 

  • Niraula A, Wang Y, Godbout JP, Sheridan JF (2018) Corticosterone production during repeated social defeat causes monocyte mobilization from the bone marrow, glucocorticoid resistance, and neurovascular adhesion molecule expression. J Neurosci 38(9):2328–2340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nizri E, Amitay YH, Sicsic C, Lavon I, Brenner T (2006) Anti-inflammatory properties of cholinergic up-regulation: a new role for acetylcholinesterase inhibitors. Neuropharmacology 50(5):540–547

    Article  CAS  PubMed  Google Scholar 

  • Norden DM, Muccigrosso MM, Godbout JP (2015) Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease. Neuropharmacology 96:29–41

    Article  CAS  PubMed  Google Scholar 

  • Nuss P (2015) Anxiety disorders and GABA neurotransmission: a disturbance of modulation. Neuropsychiatr Dis Treat 11:165

    PubMed  PubMed Central  Google Scholar 

  • Oboh G, Ademosun AO, Akinleye M, Omojokun OS, Boligon AA, Athayde ML (2015) Starch composition, glycemic indices, phenolic constituents, and antioxidative and antidiabetic properties of some common tropical fruits. J Ethnic Foods 2(2):64–73

    Article  Google Scholar 

  • Okoh L, Ajayi AM, Ben-Azu B, Akinluyi ET, Emokpae O, Umukoro S (2020) d-Ribose–l-cysteine exhibits adaptogenic-like activity through inhibition of oxido-inflammatory responses and increased neuronal caspase-3 activity in mice exposed to unpredictable chronic mild stress. Mol Biol Rep 47(10):7709–7722

    Article  CAS  PubMed  Google Scholar 

  • Oladapo OM, Ben-Azu B, Ajayi AM, Emokpae O, Eneni AEO, Omogbiya IA, Iwalewa EO (2021) Naringin confers protection against psychosocial defeat stress-induced neurobehavioral deficits in mice: involvement of glutamic acid decarboxylase isoform-67, oxido-nitrergic stress, and neuroinflammatory mechanisms. J Mol Neurosci 71(3):431–445

    Article  CAS  PubMed  Google Scholar 

  • Olaniran AF, Taiwo AE, Bamidele OP, Iranloye YM, Malomo AA, Olaniran OD (2021) The role of nutraceutical fruit drink on neurodegenerative diseases: a review. Int J Food Sci Technol 57:1442–1450

    Article  Google Scholar 

  • Panossian AG, Efferth T, Shikov AN, Pozharitskaya ON, Kuchta K, Mukherjee PK, Banerjee S, Heinrich M, Wu W, Guo DA, Wagner H (2021) Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress-and aging-related diseases. Med Res Rev 41(1):630–703

    Article  PubMed  Google Scholar 

  • Patki G, Solanki N, Atrooz F, Allam F, Salim S (2013) Depression, anxiety-like behavior and memory impairment are associated with increased oxidative stress and inflammation in a rat model of social stress. Brain Res 1539:73–86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peng X, Luo Z, He S, Zhang L, Li Y (2021) Blood-Brain Barrier Disruption by Lipopolysaccharide and Sepsis-Associated Encephalopathy. Front Cell Infect Microbiol 11:1083

    Article  Google Scholar 

  • Rahman I, Kode A, Biswas SK (2006) Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nat Protoc 1(6):3159–3165

    Article  CAS  PubMed  Google Scholar 

  • Reader BF, Jarrett BL, McKim DB, Wohleb ES, Godbout JP, Sheridan JF (2015) Peripheral and central effects of repeated social defeat stress: Monocyte trafficking, microglial activation, and anxiety. Neuroscience 289:429–442. https://doi.org/10.1016/j.neuroscience.2015.01.001

    Article  CAS  PubMed  Google Scholar 

  • Rosas-Ballina M, Tracey KJ (2009) Cholinergic control of inflammation. J Intern Med 265(6):663–679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sayago-Ayerdi S, García-Martínez DL, Ramírez-Castillo AC, Ramírez-Concepción HR, Viuda-Martos M (2021) Tropical fruits and their co-products as bioactive compounds and their health effects: A review. Foods 8:1952

    Article  Google Scholar 

  • Subash S, Essa MM, Al-Adawi S, Memon MA, Manivasagam T, Akbar M (2014) Neuroprotective effects of berry fruits on neurodegenerative diseases. Neural Regen Res 9(16):1557

    Article  PubMed  PubMed Central  Google Scholar 

  • Szpręgiel I, Wrońska D, Kmiecik M, Pałka S, Kania BF (2021) Glutamic acid decarboxylase concentration changes in response to stress and altered availability of glutamic acid in rabbit (Oryctolagus cuniculus) brain limbic structures. Animals 11(2):455

    Article  PubMed  PubMed Central  Google Scholar 

  • Tang W, Li W, Yang Y, Lin X, Wang L, Li C, Yang R (2021) Phenolic compounds profile and antioxidant capacity of pitahaya fruit peel from two red-skinned species (Hylocereus polyrhizus and Hylocereus undatus). Foods 10(6):1183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trebaticka J, Ďuračková Z (2015) Psychiatric disorders and polyphenols: can they be helpful in therapy? Oxid Med Cell longev 2015:1

    Article  Google Scholar 

  • Trullas R, Skolnick P (1993) Differences in fear motivated behaviors among inbred mouse strains. Psychopharmacology 111(3):323–331

    Article  CAS  PubMed  Google Scholar 

  • Tyagi E, Agrawal R, Nath C, Shukla R (2008) Influence of LPS-induced neuroinflammation on acetylcholinesterase activity in rat brain. J Neuroimmunol 205:51–56

    Article  CAS  PubMed  Google Scholar 

  • Umukoro S, Kalejaye HA, Ben-Azu B, Ajayi AM (2018) Naringenin attenuates behavioral derangements induced by social defeat stress in mice via inhibition of acetylcholinesterase activity, oxidative stress and release of pro-inflammatory cytokines. Biomed Pharmacother 105:714–723

    Article  CAS  PubMed  Google Scholar 

  • von Dawans B, Trueg A, Kirschbaum C, Fischbacher U, Heinrichs M (2018) Acute social and physical stress interact to influence social behavior: The role of social anxiety. PLoS ONE 13(10):e0204665

    Article  Google Scholar 

  • Wallace TC, Bailey RL, Blumberg JB, Burton-Freeman B, Chen CO, Crowe-White KM, Drewnowski A, Hooshmand S, Johnson E, Lewis R, Murray R (2020) Fruits, vegetables, and health: A comprehensive narrative, umbrella review of the science and recommendations for enhanced public policy to improve intake. Crit Rev Food Sci Nutr 60(13):2174–2211

    Article  CAS  PubMed  Google Scholar 

  • Wang W, Li S, Dong HP, Lv S, Tang YY (2009) Differential impairment of spatial and nonspatial cognition in a mouse model of brain aging. Life Sci 85(3–4):127–135

    Article  CAS  PubMed  Google Scholar 

  • Weber MD, Godbout JP, Sheridan JF (2017) Repeated social defeat, neuroinflammation, and behavior: monocytes carry the signal. Neuropsychopharmacology 42(1):46–61

    Article  PubMed  Google Scholar 

  • Wohleb ES, Fenn AM, Pacenta AM, Powell ND, Sheridan JF, Godbout JP (2012) Peripheral innate immune challenge exaggerated microglia activation, increased the number of inflammatory CNS macrophages, and prolonged social withdrawal in socially defeated mice. Psychoneuroendocrinology 37(9):1491–1505. https://doi.org/10.1016/j.psyneuen.2012.02.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang H, Qu Z, Zhang J, Huo L, Gao J, Gao W (2016) Ferulic acid ameliorates memory impairment in d-galactose-induced aging mouse model. Int J Food Sci Nutr 67(7):806–817

    Article  CAS  PubMed  Google Scholar 

  • Yaribeygi H, Panahi Y, Sahraei H, Johnston TP, Sahebkar A (2017) The impact of stress on body function: A review. EXCLI J 16:1057

    PubMed  PubMed Central  Google Scholar 

  • Zhu Y, Klomparens EA, Guo S, Geng X (2019) Neuroinflammation caused by mental stress: the effect of chronic restraint stress and acute repeated social defeat stress in mice. Neurol Res 41:762–769

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Dr Olumayokun Olajide, Department of Pharmacy, University of Huddersfield, United Kingdom for kind support towards purchase of laboratory reagents and ELISA kits.

Author information

Authors and Affiliations

  1. Neuropharmacology Unit, Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Oyo-State, Nigeria

    Abayomi M. Ajayi, Benneth Ben-Azu, Gracious E. Ogunkolade, John Melete, Ayomide T. Oyedele & Solomon Umukoro

  2. Department of Pharmacology, Faculty of Basic Medical Sciences, College of Health Sciences, Delta State University, Abraka, Delta State, Nigeria

    Benneth Ben-Azu

Authors
  1. Abayomi M. Ajayi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Benneth Ben-Azu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gracious E. Ogunkolade
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John Melete
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ayomide T. Oyedele
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Solomon Umukoro
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AMA was conceived, designed, analysed and wrote the draft of the manuscript; BB was involved in execution, data analysis and manuscript revising; GEO and JM all participated in the execution of the study, ATO was involved in revising and editing of the final manuscript; SU was involved in the design of the study and revised the manuscript. All authors approved final manuscript.

Corresponding author

Correspondence to Abayomi M. Ajayi.

Ethics declarations

Ethical approval

The animals used in this study were handled in accordance with the National Institutes of Health (NIH) Guidelines for the Care and Use of Laboratory Animals. The experimental protocol was approved by the University of Ibadan Animal Care and Use Research Ethics Committee (UI-ACUREC/17/0098).

Conflict of interest

Authors declare no conflict of interest.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ajayi, A.M., Ben-Azu, B., Ogunkolade, G.E. et al. Repeated social defeat stress exacerbates lipopolysaccharide-induced behavioural deficits in mice: ameliorative role of Chrysophyllum albidum fruit extract through anti-neuroinflammation, antioxidant and neurochemical balance. Metab Brain Dis 37, 2467–2481 (2022). https://doi.org/10.1007/s11011-022-01053-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-022-01053-x

Keywords

Search

Navigation