Skip to main content
SpringerLink
Log in

Antidepressant-Like Effects of Edaravone and Minocycline: Investigation of Oxidative Stress, Neuroinflammation, Neurotrophic, and Apoptotic Pathways

  • Research Article
  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

Depression is a very common mental disorder and mechanism that is associated with mitochondrial dysfunction. In the present study, we examined the mechanisms of action of isolated brain mitochondria in rats with depression for the first time. This will help identify the mitochondrial protective pathways of the two drugs and shed light on new therapeutic goals for developing antidepressants. Forced swimming, tail suspension, and sucrose preference tests were used to assess depressive-like behaviors and the oxidative stress factors of brain tissue, and measure the gene expression of apoptotic and anti-apoptotic, neuroplasticity, and neuroinflammatory factors by RT-PCR and acetylcholinesterase (AChE) activity in brain tissue (hippocampus and prefrontal) and the serum levels of corticosterone and fasting blood sugar. The results showed that the separation of neonatal rats from their mothers induced depressive-like behaviors, weight loss, mitochondrial dysfunction, increased expression of genes involved in neuroinflammation, apoptosis, genes involved in the depressive process, and decreased expression of genes involved in mood in both the hippocampus and prefrontal cortex. Maternal separation increased serum corticosterone levels, caused dysfunction of the cholinergic system, and also increased AChE activity. Treatment with different concentrations of minocycline and edaravone (1, 20, and 50 mg/kg), 5MTHF, and citalopram for 14 days showed that these drugs improved depression-like behaviors and mitochondrial function. It also reduced the expression of genes involved in neuroinflammation, apoptosis, and depression and increased the expression of genes involved in mood. In conclusion, minocycline and edaravone have neuroprotective, mitochondrial protective, antioxidant, anti-inflammatory, and anti-apoptotic effects against depressive-like behaviors caused by chronic stress.

Graphical Abstract

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
Fig. 10
Fig. 11
Fig. 12
Fig. 13

Similar content being viewed by others

Availability of Data and Materials

The authors confirm that the data supporting the findings of this study are available.

References

  • Ahmadinejad F, Geir Møller S, Hashemzadeh-Chaleshtori M, Bidkhori G, Jami M-S (2017) Molecular mechanisms behind free radical scavengers function against oxidative stress. Antioxidants 6(3):51

    Article  Google Scholar 

  • Allen J, Romay-Tallon R, Brymer KJ, Caruncho HJ, Kalynchuk LE (2018) Mitochondria and mood: mitochondrial dysfunction as a key player in the manifestation of depression. Front Neurosci 12:386

    Article  Google Scholar 

  • Anjomshoa M, Boroujeni SN, Ghasemi S, Lorigooini Z, Amiri A, Balali-dehkordi S et al (2020) Rutin via increase in the CA3 diameter of the hippocampus exerted antidepressant-like effect in mouse model of maternal separation stress: possible involvement of NMDA receptors. Behav Neurol 2020:4813616

    Article  Google Scholar 

  • Autry AE, Monteggia LM (2012) Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev 64(2):238–258

    Article  Google Scholar 

  • Bagheri A, Khorshid HRK, Tavallaie M, Mowla SJ, Sherafatian M, Rashidi M et al (2019) A panel of noncoding RNAs in non–small-cell lung cancer. J Cell Biochem 120(5):8280–8290

    Article  Google Scholar 

  • Bailly C, Hecquet P-E, Kouach M, Thuru X, Goossens J-F (2020) Chemical reactivity and uses of 1-phenyl-3-methyl-5-pyrazolone (PMP), also known as edaravone. Bioorg Med Chem 28(10):115463

    Article  Google Scholar 

  • Bassi GS, Kanashiro A, Santin FM, de Souza GE, Nobre MJ, Coimbra NC (2012) Lipopolysaccharide-induced sickness behaviour evaluated in different models of anxiety and innate fear in rats. Basic Clin Pharmacol Toxicol 110(4):359–369

    Article  Google Scholar 

  • Becker EB, Howell J, Kodama Y, Barker PA, Bonni A (2004) Characterization of the c-Jun N-terminal kinase-BimEL signaling pathway in neuronal apoptosis. J Neurosci 24(40):8762–8770

    Article  Google Scholar 

  • Boccia ML, Razzoli M, Prasad Vadlamudi S, Trumbull W, Caleffie C, Pedersen CA (2007) Repeated long separations from pups produce depression-like behavior in rat mothers. Psychoneuroendocrinology 32(1):65–71

    Article  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72(1):248–254

    Article  Google Scholar 

  • Brummelte S, Galea LA (2010) Chronic corticosterone during pregnancy and postpartum affects maternal care, cell proliferation and depressive-like behavior in the dam. Horm Behav 58(5):769–779

    Article  Google Scholar 

  • Buttenschøn H, Demontis D, Kaas M, Elfving B, Mølgaard S, Gustafsen C et al (2015) Increased serum levels of sortilin are associated with depression and correlated with BDNF and VEGF. Transl Psychiatry 5(11):e677-e

  • Buttenschøn HN, Elfving B, Nielsen M, Skeldal S, Kaas M, Mors O et al (2018) Exploring the sortilin related receptor, SorLA, in depression. J Affect Disord 232:260–267

    Article  Google Scholar 

  • Calabrese F, Rossetti AC, Racagni G, Gass P, Riva MA, Molteni R (2014) Brain-derived neurotrophic factor: a bridge between inflammation and neuroplasticity. Front Cell Neurosci 8:430

    Article  Google Scholar 

  • Camargos QM, Silva BC, Silva DG, Toscano ECB, Oliveira BDS, Bellozi PMQ et al (2020) Minocycline treatment prevents depression and anxiety-like behaviors and promotes neuroprotection after experimental ischemic stroke. Brain Res Bull 155:1–10

    Article  Google Scholar 

  • Cataldo AM, McPhie DL, Lange NT, Punzell S, Elmiligy S, Ye NZ et al (2010) Abnormalities in mitochondrial structure in cells from patients with bipolar disorder. Am J Pathol 177(2):575–585

    Article  Google Scholar 

  • Cline BH, Anthony DC, Lysko A, Dolgov O, Anokhin K, Schroeter C et al (2015) Lasting downregulation of the lipid peroxidation enzymes in the prefrontal cortex of mice susceptible to stress-induced anhedonia. Behav Brain Res 276:118–129

    Article  Google Scholar 

  • Corbett GT, Roy A, Pahan K (2013) Sodium phenylbutyrate enhances astrocytic neurotrophin synthesis via protein kinase C (PKC)-mediated activation of cAMP-response element-binding protein (CREB): implications for Alzheimer disease therapy. J Biol Chem 288(12):8299–8312

    Article  Google Scholar 

  • Cryan JF, Mombereau C, Vassout A (2005) The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice. Neurosci Biobehav Rev 29(4–5):571–625

    Article  Google Scholar 

  • Dean OMKB, Ashton M, Mohebbi M, Ng CH, Maes M, Berk L, Sughondhabirom A, Tangwongchai S, Singh AB, McKenzie H (2017) Adjunctive minocycline treatment for major depressive disorder: a proof of concept trial. Aust N Z J Psychiatry 8(51):829–840

    Article  Google Scholar 

  • Dimatelis J, Uys J, Marais L, Stein D, Daniels W (2007) Early maternal separation alters the response to traumatization: resulting in increased levels of hippocampal neurotrophic factors. Metab Brain Dis 22:183–195

    Article  Google Scholar 

  • Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK et al (2010) A meta-analysis of cytokines in major depression. Biol Psychiatry 67(5):446–457

    Article  Google Scholar 

  • Dubovsky S (2010) Depression is an inflammatory disease. J Watch Psychiatry 67:446

    Google Scholar 

  • Dulawa SC, Janowsky DS (2019) Cholinergic regulation of mood: from basic and clinical studies to emerging therapeutics. Mol Psychiatry 24(5):694–709

    Article  Google Scholar 

  • Duman RS (2002) Pathophysiology of depression: the concept of synaptic plasticity. European Psychiatry: the Journal of the Association of European Psychiatrists 17(Suppl 3):306–310

    Article  Google Scholar 

  • Duman RS, Malberg J, Nakagawa S, D’Sa C (2000) Neuronal plasticity and survival in mood disorders. Biol Psychiatry 48(8):732–739

    Article  Google Scholar 

  • Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82(1):70–77

    Article  Google Scholar 

  • 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  Google Scholar 

  • Farahbakhsh S, Hatef B, Akhtari Z, Bourbour Z, Sahraei H (2019) Antidepressant effect of cinnamon (Cinnamomum zeylanicum L.) water extract (CWE) evaluated by forced swimming test in mice. J Med Plants 18(70):154–61

  • Gaignard P, Liere P, Thérond P, Schumacher M, Slama A, Guennoun R (2017) Role of sex hormones on brain mitochondrial function, with special reference to aging and neurodegenerative diseases. Front Aging Neurosci 9:406-

  • Gu Z-S, Zhou A-n, Xiao Y, Zhang Q-W, Li J-Q (2018) Synthesis and antidepressant-like activity of novel aralkyl piperazine derivatives targeting SSRI/5-HT1A/5-HT7. Europ J Med Chem 144:701–15

  • Han Y, Zhang L, Wang Q, Zhang D, Zhao Q, Zhang J et al (2019) Minocycline inhibits microglial activation and alleviates depressive-like behaviors in male adolescent mice subjected to maternal separation. Psychoneuroendocrinology 107:37–45

    Article  Google Scholar 

  • Herbet M, Natorska-Chomicka D, Ostrowska M, Gawrońska-Grzywacz M, Izdebska M, Piątkowska-Chmiel I et al (2019) Edaravone presents antidepressant-like activity in corticosterone model of depression in mice with possible role of Fkbp5, Comt, Adora1 and Slc6a15 genes. Toxicol Appl Pharmacol 380:114689

    Article  Google Scholar 

  • Homsi S, Federico F, Croci N, Palmier B, Plotkine M, Marchand-Leroux C et al (2009) Minocycline effects on cerebral edema: relations with inflammatory and oxidative stress markers following traumatic brain injury in mice. Brain Res 1291:122–132

    Article  Google Scholar 

  • Jangra A, Lukhi MM, Sulakhiya K, Baruah CC, Lahkar M (2014a) Protective effect of mangiferin against lipopolysaccharide-induced depressive and anxiety-like behaviour in mice. Eur J Pharmacol 740:337–345

    Article  Google Scholar 

  • Jangra A, Datusalia AK, Sharma SS (2014b) Reversal of neurobehavioral and neurochemical alterations in STZ-induced diabetic rats by FeTMPyP, a peroxynitrite decomposition catalyst and 1,5-isoquinolinediol a poly (ADP-ribose) polymerase inhibitor. Neurol Res 36(7):619–626

    Article  Google Scholar 

  • Jangra A, Kasbe P, Pandey SN, Dwivedi S, Gurjar SS, Kwatra M et al (2015) Hesperidin and silibinin ameliorate aluminum-induced neurotoxicity: modulation of antioxidants and inflammatory cytokines level in mice hippocampus. Biol Trace Elem Res 168(2):462–471

    Article  Google Scholar 

  • Jangra A, Sriram CS, Dwivedi S, Gurjar SS, Hussain MI, Borah P et al (2017) Sodium phenylbutyrate and edaravone abrogate chronic restraint stress-induced behavioral deficits: implication of oxido-nitrosative, endoplasmic reticulum stress cascade, and neuroinflammation. Cell Mol Neurobiol 37(1):65–81

    Article  Google Scholar 

  • Janowsky DS, El-Yousef MK, Davis JM (1974) Acetylcholine and depression. Psychosom Med

  • Johnson D, Lanahan A, Buck CR, Sehgal A, Morgan C, Mercer E et al (1986) Expression and structure of the human NGF receptor. Cell 47(4):545–554

    Article  Google Scholar 

  • Kasbe P, Jangra A, Lahkar M (2015) Mangiferin ameliorates aluminium chloride-induced cognitive dysfunction via alleviation of hippocampal oxido-nitrosative stress, proinflammatory cytokines and acetylcholinesterase level. J Trace Elem Med Biol 31:107–112

    Article  Google Scholar 

  • Kim JJ, Diamond DM (2002) The stressed hippocampus, synaptic plasticity and lost memories. Nat Rev Neurosci 3(6):453–462

    Article  Google Scholar 

  • Liu Y, Gou L-S, Tian X, Fu X-B, Ling X, Sun L-Y et al (2013a) Protective effects of luteolin on cognitive impairments induced by psychological stress in mice. Exp Biol Med 238(4):418–425

    Article  Google Scholar 

  • Liu Y, Zhuang X, Gou L, Ling X, Tian X, Liu L et al (2013b) Protective effects of nizofenone administration on the cognitive impairments induced by chronic restraint stress in mice. Pharmacol Biochem Behav 103(3):474–480

    Article  Google Scholar 

  • Liu W-X, Wang J, Xie Z-M, Xu N, Zhang G-F, Jia M et al (2016) Regulation of glutamate transporter 1 via BDNF-TrkB signaling plays a role in the anti-apoptotic and antidepressant effects of ketamine in chronic unpredictable stress model of depression. Psychopharmacology 233(3):405–415

    Article  Google Scholar 

  • Lorigooini Z, Nouri A, Balali-Dehkordi S, Bijad E, Dehkordi SH, Soltani A et al (2021) Ferulic acid through mitigation of NMDA receptor pathway exerts an anxiolytic-like effect in mouse model of maternal separation stress. J Basic Clin Physiol Pharmacol 32(1)

  • Madrigal JL, Olivenza R, Moro MA, Lizasoain I, Lorenzo P, Rodrigo J et al (2001) Glutathione depletion, lipid peroxidation and mitochondrial dysfunction are induced by chronic stress in rat brain. Neuropsychopharmacology 24(4):420–429

    Article  Google Scholar 

  • Maes M, Fišar Z, Medina M, Scapagnini G, Nowak G, Berk M (2012) New drug targets in depression: inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates—Nrf2 activators and GSK-3 inhibitors. Inflammopharmacol 20(3):127–50

  • Maes M, Mihaylova I, Kubera M, Ringel K (2012) Activation of cell-mediated immunity in depression: association with inflammation, melancholia, clinical staging and the fatigue and somatic symptom cluster of depression. Prog Neuropsychopharmacol Biol Psychiatry 36(1):169–175

    Article  Google Scholar 

  • Maria Michel T, Pulschen D, Thome J (2012) The role of oxidative stress in depressive disorders. Curr Pharm Des 18(36):5890–5899

    Article  Google Scholar 

  • Michel TM, Camara S, Tatschner T, Frangou S, Sheldrick AJ, Riederer P et al (2010) Increased xanthine oxidase in the thalamus and putamen in depression. The World Journal of Biological Psychiatry 11(2–2):314–320

    Article  Google Scholar 

  • Miller AL (2008) The methylation, neurotransmitter, and antioxidant connections between folate and depression. Altern Med Rev 3(3)

  • Mitić M, Lazarević-Pašti T (2021) Does the application of acetylcholinesterase inhibitors in the treatment of Alzheimer’s disease lead to depression? Expert Opin Drug Metab Toxicol 17(7):841–856

    Article  Google Scholar 

  • Miyaoka T, Wake R, Furuya M, Liaury K, Ieda M, Kawakami K et al (2012) Minocycline as adjunctive therapy for patients with unipolar psychotic depression: an open-label study. Prog Neuropsychopharmacol Biol Psychiatry 37(2):222–226

    Article  Google Scholar 

  • Motafeghi F, Mortazavi P, Ghassemi-Barghi N, Zahedi M, Shokrzadeh M (2022) Dexamethasone as an anti-cancer or hepatotoxic. ToxicolMech Meth 1–17

  • Mozafari H, Amiri S, Mehr SE, Momeny M, Amini-khoei H, Bijani S et al (2020) Minocycline attenuates depressive-like behaviors in mice treated with the low dose of intracerebroventricular streptozotocin; the role of mitochondrial function and neuroinflammation. Mol Biol Rep 47(8):6143–6153

    Article  Google Scholar 

  • Mukherjee A, Mehta BK, Sen KK, Banerjee S (2018) Metabolic syndrome-associated cognitive decline in mice: Role of minocycline. Indian Journal of Pharmacology 50(2):61

    Article  Google Scholar 

  • Ohta M, Higashi Y, Yawata T, Kitahara M, Nobumoto A, Ishida E et al (2013) Attenuation of axonal injury and oxidative stress by edaravone protects against cognitive impairments after traumatic brain injury. Brain Res 1490:184–192

    Article  Google Scholar 

  • Okuyama S, Morita M, Sawamoto A, Terugo T, Nakajima M, Furukawa Y (2015) Edaravone enhances brain-derived neurotrophic factor production in the ischemic mouse brain. Pharmaceuticals 8(2):176–185

    Article  Google Scholar 

  • Prowse N, Dwyer Z, Thompson A, Fortin T, Elson K, Robeson H et al (2020) Early life selective knockdown of the TrkB receptor and maternal separation modulates adult stress phenotype. Behav Brain Res 378:112260

    Article  Google Scholar 

  • Radeke MJ, Misko TP, Hsu C, Herzenberg LA, Shooter EM (1987) Gene transfer and molecular cloning of the rat nerve growth factor receptor. Nature 325(6105):593–597

    Article  Google Scholar 

  • Ran Y-H, Hu X-X, Wang Y-L, Zhao N, Zhang L-M, Liu H-X et al (2018) YL-0919, a dual 5-HT1A partial agonist and SSRI, produces antidepressant-and anxiolytic-like effects in rats subjected to chronic unpredictable stress. Acta Pharmacologica Sinica 39(1):12–23

  • Salehi P, Shahmirzadi ZY, Mirrezaei FS, Shirvani Boushehri F, Mayahi F, Songhori M et al (2019) A hypothetic role of minocycline as a neuroprotective agent against methylphenidate-induced neuronal mitochondrial dysfunction and tau protein hyper-phosphorylation: Possible role of PI3/Akt/GSK3β signaling pathway. Med Hypotheses 128:6–10

    Article  Google Scholar 

  • Sato H, Takahashi T, Sumitani K, Takatsu H, Urano S (2010) Glucocorticoid generates ROS to induce oxidative injury in the hippocampus, leading to impairment of cognitive function of rats. Journal of Clinical Biochemistry and Nutrition 47(3):224–232

    Article  Google Scholar 

  • Schmidt-Kastner R, Wetmore C, Olson L (1996) Comparative study of brain-derived neurotrophic factor messenger RNA and protein at the cellular level suggests multiple roles in hippocampus, striatum and cortex. Neuroscience 74(1):161–183

    Article  Google Scholar 

  • Schroeder FA, Lin CL, Crusio WE, Akbarian S (2007) Antidepressant-like effects of the histone deacetylase inhibitor, sodium butyrate, in the mouse. Biol Psychiat 62(1):55–64

    Article  Google Scholar 

  • Shaki F, Teymoori M, Motafeghi FS, Hemmati N, Arab-Nozari M (2021) l-Arginine ameliorated mitochondrial oxidative damage induced by sub-chronic exposure to cadmium in mice kidney. Pharmaceutical and Biomedical Research 7(2):79–86

    Google Scholar 

  • Shokrzadeh M, Zamani E, Mehrzad M, Norian Y, Shaki F (2015) Protective effects of propofol against methamphetamine-induced neurotoxicity. Toxicol Int 22(1):92

    Article  Google Scholar 

  • Sinha-Hikim I, Shen R, Nzenwa I, Gelfand R, Mahata SK, Sinha-Hikim AP (2011) Minocycline suppresses oxidative stress and attenuates fetal cardiac myocyte apoptosis triggered by in utero cocaine exposure. Apoptosis 16(6):563–573

    Article  Google Scholar 

  • Stolp H, Ek C, Johansson P, Dziegielewska K, Potter A, Habgood M et al (2007) Effect of minocycline on inflammation-induced damage to the blood–brain barrier and white matter during development. Eur J Neurosci 26(12):3465–3474

    Article  Google Scholar 

  • Sulakhiya K, Kumar P, Jangra A, Dwivedi S, Hazarika NK, Baruah CC et al (2014) Honokiol abrogates lipopolysaccharide-induced depressive like behavior by impeding neuroinflammation and oxido-nitrosative stress in mice. Eur J Pharmacol 744:124–131

    Article  Google Scholar 

  • Sung Y-H, Shin M-S, Cho S, Baik H-H, Jin B-K, Chang H-K et al (2010) Depression-like state in maternal rats induced by repeated separation of pups is accompanied by a decrease of cell proliferation and an increase of apoptosis in the hippocampus. Neurosci Lett 470(1):86–90

    Article  Google Scholar 

  • Underwood CK, Coulson EJ (2008) The p75 neurotrophin receptor. Int J Biochem Cell Biol 40(9):1664–1668

    Article  Google Scholar 

  • Valipour M, Naderi N, Heidarli E, Shaki F, Motafeghi F, Talebpour Amiri F et al (2021) Design, synthesis and biological evaluation of naphthalene-derived (arylalkyl)azoles containing heterocyclic linkers as new anticonvulsants: a comprehensive in silico, in vitro, and in vivo study. Eur J Pharm Sci 166:105974

    Article  Google Scholar 

  • van Enkhuizen J, Janowsky DS, Olivier B, Minassian A, Perry W, Young JW et al (2015) The catecholaminergic–cholinergic balance hypothesis of bipolar disorder revisited. Eur J Pharmacol 753:114–126

    Article  Google Scholar 

  • Wang G, Su J, Li L, Feng J, Shi L, He W et al (2013) Edaravone alleviates hypoxia-acidosis/reoxygenation-induced neuronal injury by activating ERK1/2. Neurosci Lett 543:72–77

    Article  Google Scholar 

  • Wang D, Levine JL, Avila-Quintero V, Bloch M, Kaffman A (2020) Systematic review and meta-analysis: effects of maternal separation on anxiety-like behavior in rodents. Transl Psychiatry 10(1):1–12

    Article  Google Scholar 

  • Wells JE, Hurlbert RJ, Fehlings MG, Yong VW (2003) Neuroprotection by minocycline facilitates significant recovery from spinal cord injury in mice. Brain 126(7):1628–1637

    Article  Google Scholar 

  • Yang J, Pei Y, Pan Y-L, Jia J, Shi C, Yu Y et al (2013) Enhanced antidepressant-like effects of electroacupuncture combined with citalopram in a rat model of depression. Evidence-Based Complemen Altern Med

  • Zhang C, Zhang Y-P, Li Y-Y, Liu B-P, Wang H-Y, Li K-W et al (2019) Minocycline ameliorates depressive behaviors and neuro-immune dysfunction induced by chronic unpredictable mild stress in the rat. Behav Brain Res 356:348–357

    Article  Google Scholar 

  • Zhou L, Wu Z, Wang G, Xiao L, Wang H, Sun L et al (2020) Long-term maternal separation potentiates depressive-like behaviours and neuroinflammation in adult male C57/BL6J mice. Pharmacol Biochem Behav 196:172953

    Article  Google Scholar 

  • Zhu F, Zheng Y, Ding Y-q, Liu Y, Zhang X, Wu R et al (2014) Minocycline and risperidone prevent microglia activation and rescue behavioral deficits induced by neonatal intrahippocampal injection of lipopolysaccharide in rats. PloS One 9(4):e93966

Download references

Funding

This study was supported by a grant from the Research Council of Mazandaran University of Medical Sciences, IR.MAZUMS.REC.1399.898.

Author information

Authors and Affiliations

  1. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

    Farzaneh Motafeghi, Mohammad Seyedabadi, Fatemeh Shaki & Mohammad Shokrzadeh

  2. Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Abouzar Bagheri

  3. Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran

    Farzaneh Motafeghi, Mohammad Seyedabadi, Fatemeh Shaki & Mohammad Shokrzadeh

Authors
  1. Farzaneh Motafeghi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abouzar Bagheri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohammad Seyedabadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fatemeh Shaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohammad Shokrzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Mohammad Shokrzadeh, Abuzar Bagheri, Mohammad SeyedAbadi, and Fatmeh Shaki: contributed to conception and study design and management. Farzaneh Motafeghi: contributed to all experimental and test phases of the study, the analysis of data, the writing articles, and the drafting of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Farzaneh Motafeghi, Abouzar Bagheri or Mohammad Shokrzadeh.

Ethics declarations

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Conflict of Interest

The 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

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Motafeghi, F., Bagheri, A., Seyedabadi, M. et al. Antidepressant-Like Effects of Edaravone and Minocycline: Investigation of Oxidative Stress, Neuroinflammation, Neurotrophic, and Apoptotic Pathways. Neurotox Res 40, 1838–1858 (2022). https://doi.org/10.1007/s12640-022-00603-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12640-022-00603-6

Keywords

Search

Navigation