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Sodium Phenylbutyrate and Edaravone Abrogate Chronic Restraint Stress-Induced Behavioral Deficits: Implication of Oxido-Nitrosative, Endoplasmic Reticulum Stress Cascade, and Neuroinflammation

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Abstract

Chronic stress exposure can produce deleterious effects on the hippocampus (HC) which eventually leads to cognitive impairment and depression. Endoplasmic reticulum (ER) stress has been reported as one of the major culprits in the development of stress-induced cognitive impairment and depression. We investigated the neuroprotective efficacy of sodium phenylbutyrate (SPB), an ER stress inhibitor, and edaravone, a free radical scavenger, against chronic restraint stress (CRS)-induced cognitive deficits and anxiety- and depressive-like behavior in mice. Adult male Swiss albino mice were restrained for 6 h/day for 28 days and injected (i.p.) with SPB (40 and 120 mg/kg) or edaravone (3 and 10 mg/kg) for the last seven days. After stress cessation, the anxiety- and depressive-like behavior along with spatial learning and memory were examined. Furthermore, oxido-nitrosative stress, proinflammatory cytokines, and gene expression level of ER stress-related genes were assessed in HC and prefrontal cortex (PFC). CRS-exposed mice showed anxiety- and depressive-like behavior, which was significantly improved by SPB and edaravone treatment. In addition, SPB and edaravone treatment significantly alleviated CRS-induced spatial learning and memory impairment. Furthermore, CRS-evoked oxido-nitrosative stress, neuroinflammation, and depletion of Brain-derived neurotrophic factor were significantly ameliorated by SPB and edaravone treatment. We found significant up-regulation of ER stress-related genes in both HC and PFC regions, which were suppressed by SPB and edaravone treatment in CRS mice. Our study provides evidence that SPB and edaravone exerted neuroprotective effects on CRS-induced cognitive deficits and anxiety- and depressive-like behavior, which is possibly coupled with inhibition of oxido-nitrosative stress, neuroinflammation, and ER stress cascade.

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References

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bannerman DM, Sprengel R, Sanderson DJ, McHugh SB, Rawlins JNP, Monyer H et al (2014) Hippocampal synaptic plasticity, spatial memory and anxiety. Nat Rev Neurosci 15(3):181–192

    Article  CAS  PubMed  Google Scholar 

  • Bassi GS, Kanashiro A, Santin FM, de Souza GEP, 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  CAS  PubMed  Google Scholar 

  • Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888

    CAS  PubMed  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  PubMed  PubMed Central  Google Scholar 

  • Chaudhari N, Talwar P, Parimisetty A, d’Hellencourt CL, Ravanan P (2014) A molecular web: endoplasmic reticulum stress, inflammation, and oxidative stress. Front Cell Neurosci 8:213

    Article  PubMed  PubMed Central  Google Scholar 

  • Chiba S, Numakawa T, Ninomiya M, Richards MC, Wakabayashi C, Kunugi H (2012) Chronic restraint stress causes anxiety-and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex. Prog Neuropsychopharmacol Biol Psychiatry 39(1):112–119

    Article  CAS  PubMed  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  CAS  PubMed  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  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • García-Bueno B, Caso JR, Leza JC (2008) Stress as a neuroinflammatory condition in brain: damage and protective mechanisms. Neurosci Biobehav Rev 32(6):1136–1151

    Article  PubMed  Google Scholar 

  • Gardian G, Browne SE, Choi D-K, Klivenyi P, Gregorio J, Kubilus JK et al (2005) Neuroprotective effects of phenylbutyrate in the N171-82Q transgenic mouse model of Huntington’s disease. J Biol Chem 280(1):556–563

    Article  CAS  PubMed  Google Scholar 

  • Guan Z, Fang J (2006) Peripheral immune activation by lipopolysaccharide decreases neurotrophins in the cortex and hippocampus in rats. Brain Behav Immun 20:64–71

    Article  CAS  PubMed  Google Scholar 

  • Hayashi A, Kasahara T, Kametani M, Toyota T, Yoshikawa T, Kato T (2009) Aberrant endoplasmic reticulum stress response in lymphoblastoid cells from patients with bipolar disorder. Int J Neuropsychopharmacol 12(1):33–43

    Article  CAS  PubMed  Google Scholar 

  • Huang GB, Zhao T, Muna SS, Bagalkot TR, Jin HM, Chae HJ et al (2013) Effects of chronic social defeat stress on behaviour, endoplasmic reticulum proteins and choline acetyltransferase in adolescent mice. Int J Neuropsychopharmacol 16(7):1635–1647

    Article  CAS  PubMed  Google Scholar 

  • Huang P, Li C, Fu T, Zhao D, Yi Z, Lu Q et al (2015a) Flupirtine attenuates chronic restraint stress-induced cognitive deficits and hippocampal apoptosis in male mice. Behav Brain Res 288:1–10

    Article  CAS  PubMed  Google Scholar 

  • Huang RR, Hu W, Yin YY, Wang YC, Li WP, Li WZ (2015b) Chronic restraint stress promotes learning and memory impairment due to enhanced neuronal endoplasmic reticulum stress in the frontal cortex and hippocampus in male mice. Int J Mol Med 35(2):553–559

    CAS  PubMed  Google Scholar 

  • Ishisaka M, Kakefuda K, Yamauchi M, Tsuruma K, Shimazawa M, Tsuruta A et al (2011) Luteolin shows an antidepressant-like effect via suppressing endoplasmic reticulum stress. Biol Pharm Bull 34(9):1481–1486

    Article  CAS  PubMed  Google Scholar 

  • Itoh T, Satou T, Nishida S, Tsubaki M, Imano M, Hashimoto S et al (2010) Edaravone protects against apoptotic neuronal cell death and improves cerebral function after traumatic brain injury in rats. Neurochem Res 35(2):348–355

    Article  CAS  PubMed  Google Scholar 

  • Jangra A, Datusalia AK, Khandwe S, Sharma SS (2013) Amelioration of diabetes-induced neurobehavioral and neurochemical changes by melatonin and nicotinamide: implication of oxidative stress-“PARP pathway. Pharmacol Biochem Behav 114:43–51

    Article  PubMed  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  CAS  PubMed  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  CAS  PubMed  Google Scholar 

  • Jangra A, Dwivedi S, Sriram CS, Gurjar SS, Kwatra M, Sulakhiya K, Baruah CC, Lahkar M (2015a) Honokiol abrogates chronic restraint stress-induced cognitive impairment and depressive-like behaviour by blocking endoplasmic reticulum stress in the hippocampus of mice. Eur J Pharmacol 770:25–32

    Article  PubMed  Google Scholar 

  • Jangra A, Kasbe P, Pandey SN, Dwivedi S, Gurjar SS, Kwatra M et al (2015b) Hesperidin and silibinin ameliorate aluminum-induced neurotoxicity: modulation of antioxidants and inflammatory cytokines level in mice hippocampus. Biol Trace Elem Res 10(7):e0131178

    Google Scholar 

  • Jiao L, Zhang J, Li Z, Liu H, Chen Y, Xu S (2011) Edaravone alleviates delayed neuronal death and long-dated cognitive dysfunction of hippocampus after transient focal ischemia in Wistar rat brains. Neuroscience 182:177–183

    Article  CAS  PubMed  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  CAS  PubMed  Google Scholar 

  • Kikuchi K, Kawahara KI, Uchikado H, Miyagi N, Kuramoto T, Miyagi T et al (2011) Potential of edaravone for neuroprotection in neurologic diseases that do not involve cerebral infarction (Review). Exp Ther Med 2(5):771–775

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Kudo T, Kanemoto S, Hara H, Morimoto N, Morihara T, Kimura R et al (2008) A molecular chaperone inducer protects neurons from ER stress. Cell Death Differ 15(2):364–375

    Article  CAS  PubMed  Google Scholar 

  • Kumari B, Kumar A, Dhir A (2007) Protective effect of non-selective and selective COX-2-inhibitors in acute immobilization stress-induced behavioral and biochemical alterations. Pharmacol Rep. 59(6):699–707

    CAS  PubMed  Google Scholar 

  • Liu Y, Gou LS, Tian X, Fu XB, Ling X, Sun LY et al (2013a) Protective effects of luteolin on cognitive impairments induced by psychological stress in mice. Exp Biol Med (Maywood) 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  CAS  PubMed  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275

    CAS  PubMed  Google Scholar 

  • Lu F, Nakamura T, Toyoshima T, Liu Y, Hirooka K, Kawai N et al (2012) Edaravone, a free radical scavenger, attenuates behavioral deficits following transient forebrain ischemia by inhibiting oxidative damage in gerbils. Neurosci Lett 506(1):28–32

    Article  CAS  PubMed  Google Scholar 

  • Maes M (2008) The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuro Endocrinol Lett 29(3):287–291

    CAS  PubMed  Google Scholar 

  • McEwen BS, Magarinos ANA (1997) Stress Effects on Morphology and Function of the Hippocampusa. Ann N Y Acad Sci 821(1):271–284

    Article  CAS  PubMed  Google Scholar 

  • Nishitoh H (2012) CHOP is a multifunctional transcription factor in the ER stress response. J Biochem 151(3):217–219

    Article  CAS  PubMed  Google Scholar 

  • Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351–358

    Article  CAS  PubMed  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  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Oyadomari S, Mori M (2004) Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ 11(4):381–389

    Article  CAS  PubMed  Google Scholar 

  • Pavlovsky AA, Boehning D, Li D, Zhang Y, Fan X, Green TA (2013) Psychological stress, cocaine and natural reward each induce endoplasmic reticulum stress genes in rat brain. Neuroscience 246:160–169

    Article  CAS  PubMed  Google Scholar 

  • Pesarico AP, Stangherlin EC, Mantovani AC, Zeni G, Nogueira CW (2015) 7-Fluoro-1, 3-diphenylisoquinoline-1-amine abolishes depressive-like behavior and prefrontal cortical oxidative damage induced by acute restraint stress in mice. Physiol Behav 149:294–302

    Article  CAS  PubMed  Google Scholar 

  • Porsolt RD, Bertin A, Jalfre M (1977) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229(2):327–336

    CAS  PubMed  Google Scholar 

  • Qi X, Hosoi T, Okuma Y, Kaneko M, Nomura Y (2004) Sodium 4-phenylbutyrate protects against cerebral ischemic injury. Mol Pharmacol 66(4):899–908

    Article  CAS  PubMed  Google Scholar 

  • Radecki DT, Brown LM, Martinez J, Teyler TJ (2005) BDNF protects against stress-induced impairments in spatial learning and memory and LTP. Hippocampus 15(2):246–253

    Article  CAS  PubMed  Google Scholar 

  • Ricobaraza A, Cuadrado-Tejedor M, Pérez-Mediavilla A, Frechilla D, Del RÃo J, GarcÃa-Osta A (2009) Phenylbutyrate ameliorates cognitive deficit and reduces tau pathology in an Alzheimer’s disease mouse model. Neuropsychopharmacology 34(7):1721–1732

    Article  CAS  PubMed  Google Scholar 

  • Roy A, Ghosh A, Jana A, Liu X, Brahmachari S, Gendelman HE et al (2012) Sodium phenylbutyrate controls neuroinflammatory and antioxidant activities and protects dopaminergic neurons in mouse models of Parkinson’s disease. PLoS One 7(6):e38113

    Article  CAS  PubMed  PubMed Central  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. J Clin Biochem Nutr. 47(3):224–232

    Article  CAS  PubMed  PubMed Central  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  CAS  PubMed  Google Scholar 

  • Schönthal AH (2012) Endoplasmic reticulum stress: its role in disease and novel prospects for therapy. Scientifica 2012:857516

    Article  PubMed  PubMed Central  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 Psychiatry 62(1):55–64

    Article  CAS  PubMed  Google Scholar 

  • Shkoda A, Ruiz PA, Daniel H, Kim SC, Rogler G, Sartor RB et al (2007) Interleukin-10 blocked endoplasmic reticulum stress in intestinal epithelial cells: impact on chronic inflammation. Gastroenterology 132(1):190–207

    Article  CAS  PubMed  Google Scholar 

  • Sokka AL, Putkonen N, Mudo G, Pryazhnikov E, Reijonen S, Khiroug L et al (2007) Endoplasmic reticulum stress inhibition protects against excitotoxic neuronal injury in the rat brain. J Neurosci 27(4):901–908

    Article  CAS  PubMed  Google Scholar 

  • Srinivasan K, Sharma SS (2011) Sodium phenylbutyrate ameliorates focal cerebral ischemic/reperfusion injury associated with comorbid type 2 diabetes by reducing endoplasmic reticulum stress and DNA fragmentation. Behav Brain Res 225(1):110–116

    Article  CAS  PubMed  Google Scholar 

  • Srinivasan K, Sharma SS (2012) Edaravone offers neuroprotection in a diabetic stroke model via inhibition of endoplasmic reticulum stress. Basic Clin Pharmacol Toxicol 110(2):133–140

    Article  CAS  PubMed  Google Scholar 

  • Sriram CS, Jangra A, Gurjar SS, Hussain MI, Borah P, Lahkar M et al (2015) Poly (ADP-ribose) polymerase-1 inhibitor, 3-aminobenzamide pretreatment ameliorates lipopolysaccharide-induced neurobehavioral and neurochemical anomalies in mice. Pharmacol Biochem Behav 133:83–91

    Article  CAS  PubMed  Google Scholar 

  • Sriram CS, Jangra A, Gurjar SS, Mohan P, Bezbaruah BK (2016) Edaravone abrogates LPS-induced behavioral anomalies, neuroinflammation and PARP-1. Physiol Behav 154:135–144

    Article  CAS  PubMed  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  CAS  PubMed  Google Scholar 

  • Tabas I, Ron D (2011) Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol 13(3):184–190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takuma K, Hara Y, Kataoka S, Kawanai T, Maeda Y, Watanabe R et al (2014) Chronic treatment with valproic acid or sodium butyrate attenuates novel object recognition deficits and hippocampal dendritic spine loss in a mouse model of autism. Pharmacol Biochem Behav 126:43–49

    Article  CAS  PubMed  Google Scholar 

  • Tan H, Zou W, Jiang J, Tian Y, Xiao Z, Bi L et al (2015) Disturbance of hippocampal H2S generation contributes to CUMS-induced depression-like behavior: involvement in endoplasmic reticulum stress of hippocampus. Acta Biochim Biophys Sin (Shanghai) 2015:gmv009

    Google Scholar 

  • Tse YC, Montoya I, Wong AS, Mathieu A, Lissemore J, Lagace DC et al (2014) A longitudinal study of stress-induced hippocampal volume changes in mice that are susceptible or resilient to chronic social defeat. Hippocampus 24(9):1120–1128

    Article  PubMed  Google Scholar 

  • Vorhees CV, Williams MT (2006) Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc 1(2):848–858

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang M, Wey S, Zhang Y, Ye R, Lee AS (2009) Role of the unfolded protein response regulator GRP78/BiP in development, cancer, and neurological disorders. Antioxid Redox Signal 11(9):2307–2316

    Article  CAS  PubMed  PubMed Central  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  CAS  PubMed  Google Scholar 

  • Yuan WJ, Yasuhara T, Shingo T, Muraoka K, Agari T, Kameda M et al (2008) Neuroprotective effects of edaravone-administration on 6-OHDA-treated dopaminergic neurons. BMC neurosci 9(1):75

    Article  PubMed  Google Scholar 

  • Zhang N, Komine-Kobayashi M, Tanaka R, Liu M, Mizuno Y, Urabe T (2005) Edaravone reduces early accumulation of oxidative products and sequential inflammatory responses after transient focal ischemia in mice brain. Stroke 36(10):2220–2225

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Liu W, Zhou Y, Ma C, Li S, Cong B (2014) Endoplasmic reticulum stress is involved in restraint stress-induced hippocampal apoptosis and cognitive impairments in rats. Physiol Behav 131:41–48

    Article  CAS  PubMed  Google Scholar 

  • Zhao T, Huang G-B, Muna SS, Bagalkot TR, Jin H-M, Chae H-J et al (2013) Effects of chronic social defeat stress on behavior and choline acetyltransferase, 78-kDa glucose-regulated protein, and CCAAT/enhancer-binding protein (C/EBP) homologous protein in adult mice. Psychopharmacology 228(2):217–230

    Article  CAS  PubMed  Google Scholar 

  • Zhao Y, Yan Y, Zhao Z, Li S, Yin J (2015) The dynamic changes of endoplasmic reticulum stress pathway markers GRP78 and CHOP in the hippocampus of diabetic mice. Brain Res Bull 111:27–35

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to thank the Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Government of India, for financial support. The authors are immensely thankful to Institutional Level Biotech hub, NIPER Guwahati, and State Biotech Hub, College of Veterinary Sciences, Guwahati, for providing technical support.

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Authors and Affiliations

  1. Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, Assam, 781032, India

    Ashok Jangra, Chandra Shaker Sriram, Shubham Dwivedi & Mangala Lahkar

  2. Department of Biotechnology, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, Assam, 781032, India

    Satendra Singh Gurjar

  3. State Biotech Hub, College of Veterinary Science, Khanapara, Guwahati, Assam, 781022, India

    Md Iftikar Hussain & Probodh Borah

  4. Department of Pharmacology, Gauhati Medical College, Guwahati, Assam, 781032, India

    Mangala Lahkar

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  1. Ashok Jangra
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Correspondence to Mangala Lahkar.

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Jangra, A., Sriram, C.S., Dwivedi, S. et al. 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, 65–81 (2017). https://doi.org/10.1007/s10571-016-0344-5

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