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      <PublisherName>isfcppharmaspire</PublisherName>
      <JournalTitle>Pharmaspire</JournalTitle>
      <PISSN>C</PISSN>
      <EISSN>o</EISSN>
      <Volume-Issue>Volume 14,Issue 1 ,2022 </Volume-Issue>
      <PartNumber/>
      <IssueTopic>Multidisciplinary</IssueTopic>
      <IssueLanguage>English</IssueLanguage>
      <Season>January-March 2022 </Season>
      <SpecialIssue>N</SpecialIssue>
      <SupplementaryIssue>N</SupplementaryIssue>
      <IssueOA>Y</IssueOA>
      <PubDate>
        <Year>-0001</Year>
        <Month>11</Month>
        <Day>30</Day>
      </PubDate>
      <ArticleType>Pharmacology</ArticleType>
      <ArticleTitle>An insight on chronic unpredictable stress in association with pathophysiology, neurotransmitters, and experimental models</ArticleTitle>
      <SubTitle/>
      <ArticleLanguage>English</ArticleLanguage>
      <ArticleOA>Y</ArticleOA>
      <FirstPage>28</FirstPage>
      <LastPage>40</LastPage>
      <AuthorList>
        <Author>
          <FirstName>Bhawna</FirstName>
          <LastName>Devi</LastName>
          <AuthorLanguage>English</AuthorLanguage>
          <Affiliation/>
          <CorrespondingAuthor>N</CorrespondingAuthor>
          <ORCID/>
          <FirstName>Meena</FirstName>
          <LastName>Yadav</LastName>
          <AuthorLanguage>English</AuthorLanguage>
          <Affiliation/>
          <CorrespondingAuthor>Y</CorrespondingAuthor>
          <ORCID/>
          <FirstName>Lakshay</FirstName>
          <LastName>Kapil</LastName>
          <AuthorLanguage>English</AuthorLanguage>
          <Affiliation/>
          <CorrespondingAuthor>Y</CorrespondingAuthor>
          <ORCID/>
          <FirstName>Arti</FirstName>
          <LastName>Singh</LastName>
          <AuthorLanguage>English</AuthorLanguage>
          <Affiliation/>
          <CorrespondingAuthor>Y</CorrespondingAuthor>
          <ORCID/>
        </Author>
      </AuthorList>
      <DOI>10.56933/Pharmaspire.2022.14104</DOI>
      <Abstract>Stress is a common disorder affecting the normal functioning of the brain and behavior majorly in the prefrontal cortex and hippocampus region of the brain. Any long-term intrinsic and extrinsic stimulus evokes chronic stress-like conditions. Chronic stress reported enhancing the formation of reactive oxygen species, leading to mitochondrial cell death through the activation of the hypothalamic-pituitary axis which releases cortisol, excessive secretion of cortisol is responsible for alteration in glucose metabolism, and other neurological disorders such as anxiety, depression, multiple sclerosis, Alzheimer, and Parkinson’s disease. The purpose of this review is to provide an insight into the various pathophysiological aspects along with neurotransmitters involved in chronic stress and its association with various neurological disorders. Along with this, we also provided a background on the various experimental models of chronic stress.</Abstract>
      <AbstractLanguage>English</AbstractLanguage>
      <Keywords>Anxiety, Chronic stress, Cortisol, Experimental models, Hypothalamic-pituitary axis, Neurological disorders</Keywords>
      <URLs>
        <Abstract>https://isfcppharmaspire.com/ubijournal-v1copy/journals/abstract.php?article_id=14101&amp;title=An insight on chronic unpredictable stress in association with pathophysiology, neurotransmitters, and experimental models</Abstract>
      </URLs>
      <References>
        <ReferencesarticleTitle>References</ReferencesarticleTitle>
        <ReferencesfirstPage>16</ReferencesfirstPage>
        <ReferenceslastPage>19</ReferenceslastPage>
        <References>1. Jin P. Efficacy of Tai Chi, brisk walking, meditation, and reading in reducing mental and emotional stress. J Psychosom Res 1992;36:361-70.&#13;
2. Sun FT, Kuo C, Cheng HT, Buthpitiya S, Collins P, Griss M. Activity-aware mental stress detection using physiological sensors. In: International Conference on Mobile Computing, Applications, and Services. Berlin, Heidelberg: Springer; 2010. p. 282-301.&#13;
3. Steptoe A, Hamer M, Chida Y. The effects of acute psychological stress on circulating inflammatory factors in humans: A review and meta-analysis. Brain Behav Immun 2007;21:901-12.&#13;
4. Vyas A, Mitra R, Shankaranarayana Rao BS, Chattarji S. Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. J Neurosci 2002;22:6810-8.&#13;
5. Gibbons C, Dempster M, Moutray M. Stress and eustress in nursing students. J Adv Nurs 2008;61:282-90.&#13;
6. Ridner SH. Psychological distress: Concept analysis. J Adv Nurs 2004;45:536-45.&#13;
7. Hammen C. Stress and depression. Annu Rev Clin Psychol 2005;1:293-319.&#13;
8. Liu D, Wang Z, Gao Z, Xie K, Zhang Q, Jiang H, et al. Effects of curcumin on learning and memory deficits, BDNF, and ERK protein expression in rats exposed to chronic unpredictable stress. Behav Brain Res 2014;271:116-21.&#13;
9. Cremaschi GA, Gorelik G, Klecha AJ, Lysionek AE, Genaro AM. Chronic stress influences the immune system through the thyroid axis. Life Sci 2000;67:3171-9.&#13;
10. Fevre ML, Matheny J, Kolt GS. Eustress, distress, and interpretation in occupational stress. J Manag Psychol 2003;18:726-44.&#13;
11. Archer T, Rapp-Ricciardi M. Stress, Affective Status and Neurodegenerative Onslaughts. In: Personality and Brain Disorders. Berlin: Springer; 2019. p. 41-58.&#13;
12. Murthy RS. National mental health survey of India 2015- 2016. Indian J Psychiatry 2017;59:21-6.&#13;
13. Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res 2002;53:865-71.&#13;
14. Selhub E. Mind-body medicine for treating depression: Using the mind to alter the body’s response to stress. Altern Complement Ther 2007;13:4-9.&#13;
15. Hannibal KE, Bishop MD. Chronic stress, cortisol dysfunction, and pain: A psychoneuroendocrine rationale for stress management in pain rehabilitation. Phys Ther 2014;94:1816-25.&#13;
16. Steenbergen PJ, Richardson MK, Champagne DL. The use of the zebrafish model in stress research. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:1432-51.&#13;
17. Miller DB, O’Callaghan JP. Neuroendocrine aspects of the response to stress. Metabolism 2002;51:5-10.&#13;
18. Nair A, Bonneau RH. Stress-induced elevation of glucocorticoids increases microglia proliferation through NMDA receptor activation. J Neuroimmunol 2006;171:72-85.&#13;
19. Pavlidis M, Theodoridi A, Tsalafouta A. Neuroendocrine regulation of the stress response in adult zebrafish, Danio rerio. Prog Neuropsychopharmacol Biol Psychiatry 2015;60:121-31.&#13;
20. Marketon JI, Glaser R. Stress hormones and immune function. Cell Immunol 2008;252:16-26.&#13;
21. Johnson JD, Campisi J, Sharkey CM, Kennedy SL, Nickerson M, Greenwood BN, et al. Catecholamines mediate stress-induced increases in peripheral and central inflammatory cytokines. Neuroscience 2005;135:1295-307.&#13;
22. Blackburn-Munro G, Blackburn-Munro RE. Chronic pain, chronic stress and depression: Coincidence or consequence? J Neuroendocrinol 2001;13:1009-23.&#13;
23. Tynan RJ, Naicker S, Hinwood M, Nalivaiko E, Buller KM, Pow DV, et al. Chronic stress alters the density and morphology of microglia in a subset of stress-responsive brain regions. Brain Behav Immun 2010;24:1058-68.&#13;
24. Perry VH, Nicoll JA, Holmes C. Microglia in neurodegenerative disease. Nat Rev Neurol 2010;6:193-201.&#13;
25. Kettenmann H, Hanisch UK, Noda M, Verkhratsky A. Devi, et al.: Chronic unpredictable stress and its pathology Pharmaspire | Vol. 14 | No. 1 | 2022 36 Physiology of microglia. Physiol Rev 2011;91:461-553.&#13;
26. Liu M, Li J, Dai P, Zhao F, Zheng G, Jing J, et al. Microglia activation regulates GluR1 phosphorylation in chronic unpredictable stress-induced cognitive dysfunction. Stress 2015;18:96-106.&#13;
27. Bian Y, Pan Z, Hou Z, Huang C, Li W, Zhao B. Learning, memory, and glial cell changes following recovery from chronic unpredictable stress. Brain Res Bull 2012;88:471-6.&#13;
28. Wohleb ES, Terwilliger R, Duman CH, Duman RS. Stress-induced neuronal colony stimulating factor 1 provokes microglia-mediated neuronal remodeling and depressive-like behavior. Biol Psychiatry 2018;83:38-49.&#13;
29. McMillan PJ, Wilkinson CW, Greenup L, Raskind MA, Peskind ER, Leverenz JB. Chronic cortisol exposure promotes the development of a GABAergic phenotype in the primate hippocampus. J Neurochem 2004;91:843-51.&#13;
30. Li SX, Han Y, Xu LZ, Yuan K, Zhang RX, Sun CY, et al. Uncoupling DAPK1 from NMDA receptor GluN2B subunit exerts rapid antidepressant-like effects. Mol Psychiatry 2018;23:597-608.&#13;
31. Berton O, McClung CA, Dileone RJ, Krishnan V, Renthal W, Russo SJ, et al. Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 2006;311:864-8.&#13;
32. Yadid G, Overstreet DH, Zangen A. Limbic dopaminergic adaptation to a stressful stimulus in a rat model of depression. Brain Res 2001;896:43-7.&#13;
33. Rygula R, Abumaria N, Fland;uuml;gge G, Fuchs E, Rand;uuml;ther E, Havemann-Reinecke U. Anhedonia and motivational deficits in rats: Impact of chronic social stress. Behav Brain Res 2005;162:127-34.&#13;
34. Mizoguchi K, Yuzurihara M, Ishige A, Sasaki H, Chui DH, Tabira T. Chronic stress induces impairment of spatial working memory because of prefrontal dopaminergic dysfunction. J Neurosci 2000;20:1568-74.&#13;
35. Cuadra G, Zurita A, Gioino G, Molina V. Influence of different antidepressant drugs on the effect of chronic variable stress on restraint-induced dopamine release in frontal cortex. Neuropsychopharmacology 2001;25:384-94.&#13;
36. Rasheed N, Ahmad A, Pandey CP, Chaturvedi RK, Lohani M, Palit G. Differential response of central dopaminergic system in acute and chronic unpredictable stress models in rats. Neurochem Res 2010;35:22-32.&#13;
37. Sugama S, Sekiyama K, Kodama T, Takamatsu Y, Takenouchi T, Hashimoto M. Chronic restraint stress triggers dopaminergic and noradrenergic neurodegeneration: Possible role of chronic stress in the onset of Parkinson’s&#13;
disease. Brain Behav Immun 2016;51:39-46.&#13;
38. Ahmad A, Rasheed N, Banu N, Palit G. Alterations in monoamine levels and oxidative systems in frontal cortex, striatum, and hippocampus of the rat brain during chronic unpredictable stress. Stress 2010;13:355-64.&#13;
39. Cox BM, Alsawah F, McNeill PC, Galloway MP, Perrine SA. Neurochemical, hormonal, and behavioral effects of chronic unpredictable stress in the rat. Behav Brain Res 2011;220:106-11.&#13;
40. Tafet GE, Idoyaga-Vargas VP, Abulafia DP, Calandria JM, Roffman SS, Chiovetta A, et al. Correlation between cortisol level and serotonin uptake in patients with chronic stress and depression. Cogn Affect Behav Neurosci 2001;1:388-93.&#13;
41. Fontella FU, Vendite DA, Tabajara AS, Porciand;uacute;ncula LO, da Silva Torres IL, Jardim FM, et al. Repeated restraint stress alters hippocampal glutamate uptake and release in the rat. Neurochem Res 2004;29:1703-9.&#13;
42. Chiba S, Numakawa T, Ninomiya M, Richards MC, Wakabayashi C, Kunugi H. 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 2012;39:112-9.&#13;
43. Yuen EY, Liu W, Karatsoreos IN, Feng J, McEwen BS, Yan Z. Acute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory. Proc Natl Acad Sci U S A 2009;106:14075-9.&#13;
44. Raudensky J, Yamamoto BK. Effects of chronic unpredictablestress and methamphetamine on hippocampal glutamate function. Brain Res 2007;1135:129-35.&#13;
45. Herman JP, Mueller NK, Figueiredo H. Role of GABA and glutamate circuitry in hypothalamo-pituitaryadrenocortical stress integration. Ann N Y Acad Sci 2004;1018:35-45.&#13;
46. Banasr M, Lepack A, Fee C, Duric V, Maldonado-Aviles J, DiLeone R, et al. Characterization of GABAergic marker expression in the chronic unpredictable stress model of depression. Chronic Stress (Thousand Oaks) 2017;1:20459.&#13;
47. Safaei M, Beitollahi H, Shishehbore MR. Simultaneous determination of epinephrine and folic acid using the&#13;
Fe 3O4@ SiO2/GR nanocomposite modified graphite. Russ J Electrochem 2018;54:851-9.&#13;
48. Krugers HJ, Hoogenraad CC, Groc L. Stress hormones and AMPA receptor trafficking in synaptic plasticity and memory. Nat Rev Neurosci 2010;11:675-81.&#13;
49. Roth KA, Mefford IM, Barchas JD. Epinephrine, norepinephrine, dopamine and serotonin: Differential effects of acute and chronic stress on regional brain amines. Brain Res 1982;239:417-24.&#13;
50. Kumar V, Singh C, Singh A. Zebrafish an experimental model of Huntington’s disease: Molecular aspects,&#13;
therapeutic targets and current challenges. Mol Biol Rep 2021;48:8181-94.&#13;
51. Patterson ZR, Ducharme R, Anisman H, Abizaid A. Altered metabolic and neurochemical responses to chronic unpredictable stressors in ghrelin receptordeficient mice. Eur J Neurosci 2010;32:632-9.&#13;
52. Konstandi M, Johnson E, Lang MA, Malamas M, Marselos M. Noradrenaline, dopamine, serotonin: Different effects of psychological stress on brain biogenic amines in mice and rats. Pharmacol Res 2000;41:341-6.&#13;
53. Chen Y, Michaelis M, Janig W, Devor M. Adrenoreceptor subtype mediating sympathetic-sensory coupling in injured sensory neurons. J Neurophysiol 1996;76:3721-30.&#13;
54. Gold MS, Dastmalchi S, Levine JD. and;alpha;2-Adrenergic receptor subtypes in rat dorsal root and superior cervical ganglion neurons. Pain 1997;69:179-90.&#13;
55. Chrousos GP. Stress and disorders of the stress system. Devi, et al.: Chronic unpredictable stress and its pathology 37 Pharmaspire | Vol. 14 | No. 1 | 2022 Nat Rev Endocrinol 2009;5:374-81.&#13;
56. Zimmermann FF, Altenhofen S, Kist LW, Leite CE, Bogo MR, Cognato GP, et al. Unpredictable chronic stress alters adenosine metabolism in zebrafish brain. Mol Neurobiol 2016;53:2518-28.&#13;
57. Cunha GM, Canas PM, Oliveira CR, Cunha RA. Increased density and synapto-protective effect of adenosine A2A receptors upon sub-chronic restraint stress. Neuroscience 2006;141:1775-81.&#13;
58. Crema LM, Pettenuzzo LF, Schlabitz M, Diehl L, Hoppe J, Mestriner R, et al. The effect of unpredictable chronic mild stress on depressive-like behavior and on hippocampal A1 and striatal A2A adenosine receptors. Physiol Behav 2013;109:1-7.&#13;
59. da Silva Torres IL, Bonan CD, Crema L, De Leon Nunes M, Battastini AM, Sarkis JJ, et al. Effect of drugs active at adenosine receptors upon chronic stress-induced hyperalgesia in rats. Eur J Pharmacol 2003;481:197-201.&#13;
60. Chakravarty S, Reddy BR, Sudhakar SR, Saxena S, Das T, Meghah V, et al. Chronic unpredictable stress (CUS)- induced anxiety and related mood disorders in a zebrafish model: Altered brain proteome profile implicates mitochondrial dysfunction. PLoS One 2013;8:e63302.&#13;
61. Murakami S, Imbe H, Morikawa Y, Kubo C, Senba E. Chronic stress, as well as acute stress, reduces BDNF mRNA expression in the rat hippocampus but less robustly. Neurosci Res 2005;53:129-39.&#13;
62. Numakawa T, Kumamaru E, Adachi N, Yagasaki Y, Izumi A, Kunugi H. Glucocorticoid receptor interaction with TrkB promotes BDNF-triggered PLC-and;gamma; signaling for glutamate release via a glutamate transporter. Proc Natl Acad Sci 2009;106:647-52.&#13;
63. Taliaz D, Loya A, Gersner R, Haramati S, Chen A, Zangen A. Resilience to chronic stress is mediated by hippocampal brain-derived neurotrophic factor. J Neurosci 2011;31:4475-83.&#13;
64. Schmidt MV, Scharf SH, Sterlemann V, Ganea K, Liebl C, Holsboer F. High susceptibility to chronic social stress is associated with a depression like&#13;
phenotype. Psychoneuroendocrinology 2010;35:635-43.&#13;
65. Cheng LL, Wang SJ, Gean PW. Serotonin depresses excitatory synaptic transmission and depolarizationevoked Ca2+ influx in rat basolateral amygdala via 5-HT1A receptors. Eur J Neurosci 1998;10:2163-72.&#13;
66. Bondi CO, Jett JD, Morilak DA. Beneficial effects of desipramine on cognitive function of chronically stressed rats are mediated by and;alpha;1-adrenergic receptors in medial prefrontal cortex. Prog Neuropsychopharmacol Biol Psychiatry 2010;34:913-23.&#13;
67. Aghajanian GK, Marek GJ. Serotonin, via 5-HT2A receptors, increases EPSCs in layer V pyramidal cells of prefrontal cortex by an asynchronous mode of glutamate release. Brain Res 1999;825:161-71.&#13;
68. Lapiz-Bluhm MD, Soto-Piand;ntilde;a AE, Hensler JG, Morilak DA. Chronic intermittent cold stress and serotonin depletion induce deficits of reversal learning in an attentional set-shifting test in rats. Psychopharmacology (Berl) 2009;202:329-41.&#13;
69. Bari A, Theobald DE, Caprioli D, Mar AC, Aidoo-Micah A, Dalley JW, et al. Serotonin modulates sensitivity to reward and negative feedback in a probabilistic reversal learning task in rats. Neuropsychopharmacology 2010;35:1290-301.&#13;
70. Bondi CO, Rodriguez G, Gould GG, Frazer A, Morilak DA. Chronic unpredictable stress induces a cognitive deficit and anxiety-like behavior in rats that is prevented by chronic antidepressant drug treatment. Neuropsychopharmacology 2008;33:320-31.&#13;
71. Shekhar A, Truitt W, Rainnie D, Sajdyk T. Role of stress, corticotrophin releasing factor (CRF) and amygdala plasticity in chronic anxiety. Stress 2005;8:209-19.&#13;
72. Lissek S, Powers AS, McClure EB, Phelps EA, Woldehawariat G, Grillon C, et al. Classical fear conditioning in the anxiety disorders: A meta-analysis. Behav Res Ther 2005;43:1391-424.&#13;
73. Labuschagne I, Phan KL, Wood A, Angstadt M, Chua P, Heinrichs M, et al. Oxytocin attenuates amygdala reactivity to fear in generalized social anxiety disorder. Neuropsychopharmacology 2010;35:2403-13.&#13;
74. Graeff FG, Guimarand;atilde;es FS, De Andrade TG, Deakin JF. Role of 5-HT in stress, anxiety, and depression. Pharmacol Biochem Behav 1996;54:129-41.&#13;
75. Fossat P, Bacquand;eacute;-Cazenave J, De Deurwaerdand;egrave;re P, Cattaert D, Delbecque JP. Serotonin, but not dopamine, controls the stress response and anxiety-like behavior in the crayfish Procambarus clarkii. J Exp Biol 2015;218:2745-52.&#13;
76. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H. Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science 2003;301:386-9.&#13;
77. Anisman H, Zacharko RM. Depression: The predisposing influence of stress. Behav Brain Sci 1982;5:89-99.&#13;
78. Yang L, Zhao Y, Wang Y, Liu L, Zhang X, Li B, et al. The effects of psychological stress on depression. Curr Neuropharmacol 2015;13:494-504.&#13;
79. Holm MM, Nieto?Gonzalez JL, Vardya I, Henningsen K, Jayatissa MN, Wiborg O, et al. Hippocampal GABAergic dysfunction in a rat chronic mild stress model of depression. Hippocampus 2011;21:422-33.&#13;
80. Vand;aacute;squez CE, Riener R, Reynolds E, Britton GB. NMDA receptor dysregulation in chronic state: A possible mechanism underlying depression with BDNF downregulation. Neurochem Int 2014;79:88-97.&#13;
81. Joand;euml;ls M, Karst H, Alfarez D, Heine VM, Qin Y, Riel EV. Effects of chronic stress on structure and cell function in rat hippocampus and hypothalamus. Stress 2004;7:221-31.&#13;
82. Kendell SF, Krystal JH, Sanacora G. GABA and glutamate systems as therapeutic targets in depression and mood disorders. Expert Opin Ther Targets 2005;9:153-68.&#13;
83. Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. Parkinson disease. Nat Rev Dis Primers 2017;3:17013.&#13;
84. Monzani E, Nicolis S, Dell’Acqua S, Capucciati A, Bacchella C, Zucca FA, et al. Dopamine, oxidative stress and protein-quinone modifications in Parkinson’s and other neurodegenerative diseases. Angew Chem Int Ed Engl 2019;58:6512-27.&#13;
85. Cantus DS, Land;oacute;pez NS, Ballester MC, Gand;oacute;mez SS, de la Devi, et al.: Chronic unpredictable stress and its pathology Pharmaspire | Vol. 14 | No. 1 | 2022 38 Rubia Ortand;iacute; JE. Stress in Parkinson’s disease. Cortisol and amylase biomarkers. Systematic review. Rev Cien Soc Enferm Neurol (Engl ED) 2019;1:12-22.&#13;
86. Smith LK, Jadavji NM, Colwell KL, Katrina Perehudoff S, Metz GA. Stress accelerates neural degeneration and exaggerates motor symptoms in a rat model of Parkinson’s disease. Eur J Neurosci 2008;27:2133-46.&#13;
87. Mori S, Sugama S, Nguyen W, Michel T, Sanna MG, Sanchez-Alavez M. Lack of interleukin-13 receptor and;alpha;1 delays the loss of dopaminergic neurons during chronic stress. J Neuroinflammation 2017;14:1-10.&#13;
88. Ehlers CL, Henriksen SJ, Wang M, Rivier J, Vale W, Bloom FE. Corticotropin releasing factor produces increases in brain excitability and convulsive seizures in rats. Brain Res 1983;278:332-6.&#13;
89. MacKenzie G, Maguire J. Chronic stress shifts the GABA reversal potential in the hippocampus and increases seizure susceptibility. Epilepsy Res 2015;109:13-27.&#13;
90. Billups B, Rossi D, Oshima T, Warr O, Takahashi M, Sarantis M, et al. Physiological and pathological operation of glutamate transporters. Prog Brain Res 1998;116:45-57.&#13;
91. Werner FM, Coveand;ntilde;as R. Classical neurotransmitters and neuropeptides involved in generalized epilepsy: A focus&#13;
on antiepileptic drugs. Curr Med Chem 2011;18:4933-48.&#13;
92. Stavropoulos I, Pervanidou P, Gnardellis C, Loli N, Theodorou V, Mantzou A, et al. Increased hair cortisol and antecedent somatic complaints in children with a first epileptic seizure. Epilepsy Behav 2017;68:146-52.&#13;
93. van Campen JS, Jansen FE, de Graan PN, Braun KP, Joels M. Early life stress in epilepsy: A seizure precipitant and risk factor for epileptogenesis. Epilepsy Behav 2014;38:160-71.&#13;
94. Haut SR, Vouyiouklis M, Shinnar S. Stress and epilepsy: A patient perception survey. Epilepsy Behav 2003;4:511-4.&#13;
95. Vishnoi S, Raisuddin S, Parvez S. Glutamate excitotoxicity and oxidative stress in epilepsy: Modulatory role of melatonin. J Environ Pathol Toxicol Oncol 2016;35:365-74.&#13;
96. Nelson PT, Soma LA, Lavi E. Microglia in diseases of the central nervous system. Ann Med 2002;34:491-500.&#13;
97. Sand;auml;ttler MB, Merkler D, Maier K, Stadelmann C, Ehrenreich H, Band;auml;hr M, et al. Neuroprotective effects and intracellular signaling pathways of erythropoietin in a rat model of multiple sclerosis. Cell Death Differ 2004;11 Suppl 2:S181-92.&#13;
98. Heesen C, Gold SM, Hartmann S, Mladek M, Reer R, Braumann KM, et al. Endocrine and cytokine responses to standardized physical stress in multiple sclerosis. Brain Behav Immun 2003;17:473-81.&#13;
99. Gonsette RE. Neurodegeneration in multiple sclerosis: The role of oxidative stress and excitotoxicity. J Neurol Sci 2008;274:48-53.&#13;
100. Ennis GE, An Y, Resnick SM, Ferrucci L, O’Brien RJ, Moffat SD. Long-term cortisol measures predict Alzheimer disease risk. Neurology 2017;88:371-8.&#13;
101. Wirth M, Lange C, Huijbers W, Alzheimer’s Disease Neuroimaging Initiative. Plasma cortisol is associated with cerebral hypometabolism across the Alzheimer’s disease spectrum. Neurobiol Aging 2019;84:80-9.&#13;
102. Giubilei F, Patacchioli FR, Antonini G, Monti MS, Tisei P, Bastianello S, et al. Altered circadian cortisol secretion in Alzheimer’s disease: Clinical and neuroradiological aspects. J Neurosci Res 2001;66:262-5.&#13;
103. Furcila D, DeFelipe J, Alonso-Nanclares L. Selective distribution of neurofibrillary tangles and amyloid plaques in the hippocampus of patients with Alzheimer’s Disease: A stereological approach. Front Neuroanat 2019;13:99-115.&#13;
104. Kontush A, Berndt C, Weber W, Akopyan V, Arlt S, Schippling S, et al. Amyloid-and;beta; is an antioxidant for lipoproteins in cerebrospinal fluid and plasma. Free Radic Biol Med 2001;30:119-28.&#13;
105. Wood WG, Schroeder F, Igbavboa U, Avdulov NA, Chochina SV. Brain membrane cholesterol domains, aging and amyloid beta-peptides. Neurobiol Aging 2002;23:685-94.&#13;
106. Dong H, Csernansky JG. Editorial: Stress and its impact on Alzheimer’s Disease. Neurobiol Stress 2019;10:100167.&#13;
107. Richter L, Munter LM, Ness J, Hildebrand PW, Dasari M, Unterreitmeier S, et al. Amyloid beta 42 peptide (Aand;beta;42)- lowering compounds directly bind to Aand;beta; and interfere with amyloid precursor protein (APP) transmembrane dimerization. Proc Natl Acad Sci 2010;107:14597-602.&#13;
108. Dickson DW. Apoptotic mechanisms in Alzheimer neurofibrillary degeneration: Cause or effect? J Clin Invest 2004;114:23-7.&#13;
109. Tran TT, Srivareerat M, Alkadhi KA. Chronic psychosocial stress triggers cognitive impairment in a novel at-risk model of Alzheimer’s disease. Neurobiol Dis 2010;37:756-63.&#13;
110. Catania C, Sotiropoulos I, Silva R, Onofri C, Breen KC, Sousa N, et al.The amyloidogenic potential and behavioral correlates of stress. Mol Psychiatry 2009;14:95-105.&#13;
111. Patchev VK, Patchev AV. Experimental models of stress. Dialogues Clin Neurosci 2022;8:145-57.&#13;
112. Rotzinger S, Lovejoy DA, Tan LA. Behavioral effects of neuropeptides in rodent models of depression and anxiety. Peptides 2010;31:736-56.&#13;
113. Dallman MF, Akana SF, Bhatnagar S, Bell ME, Choi S, Chu A, et al. Starvation: Early signals, sensors, and sequelae. Endocrinology 1999;140:4015-23.&#13;
114. Kiss A, Jezova D, Aguilera G. Activity of the hypothalamic pituitary adrenal axis and sympathoadrenal system during food and water deprivation in the rat. Brain Res 1994;663:84-92.&#13;
115. Brown DR, Holtzman SG. Suppression of deprivationinduced food and water intake in rats and mice by naloxone. Pharmacol Biochem Behav 1979;11:567-73.&#13;
116. McLaughlin KJ, Gomez JL, Baran SE, Conrad CD. The effects of chronic stress on hippocampal morphology and function: An evaluation of chronic restraint paradigms. Brain Res 2007;1161:56-64.&#13;
117. Jeong JY, Lee DH, Kang SS. Effects of chronic restraint stress on body weight, food intake, and hypothalamic gene expressions in mice. Endocrinol Metab 2013;28:288-96.&#13;
118. Torres IL, Gamaro GD, Vasconcellos AP, Silveira R, Dalmaz C. Effects of chronic restraint stress on feeding behavior and on monoamine levels in different brain structures in rats. Neurochem Res 2002;27:519-25. Devi, et al.: Chronic unpredictable stress and its pathology 39 Pharmaspire | Vol. 14 | No. 1 | 2022&#13;
119. Conrad CD, LeDoux JE, Magariand;ntilde;os AM, McEwen BS. Repeated restraint stress facilitates fear conditioning independently of causing hippocampal CA3 dendritic atrophy. Behav Neurosci 1999;113:902-13.&#13;
120. Galea LA, McEwen BS, Tanapat P, Deak T, Spencer RL, Dhabhar FS. Sex differences in dendritic atrophy of CA3 pyramidal neurons in response to chronic restraint stress. Neuroscience 1997;81:689-97.&#13;
121. Fukuhara K, Kvetnansky R, Cizza G, Pacak K, Ohara H, Goldstein DS, et al. Interrelations between sympathoadrenal system and hypothalamo-pituitaryadrenocortical/thyroid systems in rats exposed to cold stress. J Neuroendocrinol 1996;8:533-41.&#13;
122. Venditti P, De Rosa R, Portero-Otin M, Pamplona R, Di Meo S. Cold-induced hyperthyroidism produces oxidative damage in rat tissues and increases susceptibility to oxidants. Int J Biochem Cell Biol 2004;36:1319-31.&#13;
123. Sharma HS, Kiyatkin EA, Patnaik R, Lafuente JV, Muresanu DF, Sjand;ouml;quist PO, et al. Exacerbation of methamphetamine neurotoxicity in cold and hot environments: Neuroprotective effects of an antioxidant compound H-290/51. Mol Neurobiol 2015;52:1023-33.&#13;
124. Schrijver NC, Pallier PN, Brown VJ, Wand;uuml;rbel H. Double dissociation of social and environmental stimulation on spatial learning and reversal learning in rats. Behav Brain Res 2004;152:307-14.&#13;
125. Koike H, Ibi D, Mizoguchi H, Nagai T, Nitta A, Takuma K, et al. Behavioral abnormality and pharmacologic response in social isolation-reared mice.&#13;
Behav Brain Res 2009;202:114-21.&#13;
126. Malkesman O, Maayan R, Weizman A, Weller A. Aggressive behavior and HPA axis hormones after social isolation in adult rats of two different genetic animal models for depression. Behav Brain Res 2006;175:408-14.&#13;
127. Lukkes JL, Mokin MV, Scholl JL, Forster GL. Adult rats exposed to early-life social isolation exhibit increased anxiety and conditioned fear behavior, and altered hormonal stress responses. Horm Behav 2009;55:248-56.&#13;
128. Pijlman FT, Herremans AH, van de Kieft J, Kruse CG, van Ree JM. Behavioural changes after different stress paradigms: Prepulse inhibition increased after physical, but not emotional stress. Eur Neuropsychopharmacol 2003;13:369-80.&#13;
129. Louvart H, Maccari S, Ducrocq F, Thomas P, Darnaudand;eacute;ry M. Long-term behavioural alterations in female rats after a single intense footshock followed by situational reminders. Psychoneuroendocrinology 2005;30:316-24.&#13;
130. Daviu N, Fuentes S, Nadal R, Armario A. A single footshock causes long-lasting hypoactivity in unknown environments that is dependent on the development of contextual fear conditioning. Neurobiol Learn Mem 2010;94:183-90.&#13;
131. Yamano Y, Yoshioka M, Toda Y, Oshida Y, Chaki S, Hamamoto K, et al. Regulation of CRF, POMC and MC4R gene expression after electrical foot shock stress in the rat amygdala and hypothalamus. J Vet Med Sci 2004;66:1323-7.&#13;
132. Chida Y, Sudo N, Motomura Y, Kubo C. Electric footshock stress drives TNF-alpha production in the liver of IL-6-deficient mice. Neuroimmunomodulation 2004;11:419-24.&#13;
133. Antelman SM, Szechtman H, Chin P, Fisher AE. Tail pinch-induced eating, gnawing and licking behavior in rats: Dependence on the nigrostriatal dopamine system. Brain Res 1975;99:319-37.&#13;
134. Liu YP, Tung CS, Chuang CH, Lo SM, Ku YC, et al. Tailpinch stress and REM sleep deprivation differentially affect sensorimotor gating function in modafinil-treated rats. Behav Brain Res 2011;219:98-104.&#13;
135. Yanagisawa M, Murakoshi T, Tamai S, Otsuka M. Tailpinch methodin vitroand the effects of some antinociceptive compounds. Eur J Pharmacol 1984;106:231-9.&#13;
136. Besnard A, Sahay A. Adult hippocampal neurogenesis, fear generalization, and stress. Neuropsychopharmacology 2016;41:24-44.&#13;
137. Hoffman AN, Lorson NG, Sanabria F, Foster Olive M, Conrad CD. Chronic stress disrupts fear extinction and enhances amygdala and hippocampal Fos expression in an animal model of post-traumatic stress disorder. Neurobiol Learn Mem 2014;112:139-47.&#13;
138. Milad MR, Pitman RK, Ellis CB, Gold AL, Shin LM, Lasko NB, et al. Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biol Psychiatry 2009;66:1075-82.&#13;
139. Cohen H, Liu T, Kozlovsky N, Kaplan Z, Zohar J, Mathand;eacute; AA. The neuropeptide Y (NPY)-ergic system is associated with behavioral resilience to stress exposure in an animal model of post-traumatic stress disorder. Neuropsychopharmacology 2012;37:350-63.&#13;
140. Zoladz PR, Conrad CD, Fleshner M, Diamond DM. Acute episodes of predator exposure in conjunction with chronic social instability as an animal model of posttraumatic stress disorder. Stress 2008;11:259-81.&#13;
141. Cloitre M, Stolbach BC, Herman JL, van der Kolk B, Pynoos R, Wang J, et al. A developmental approach to complex PTSD: Childhood and adult cumulative trauma as predictors of symptom complexity. J Trauma Stress 2009;22:399-408.&#13;
142. Bencan Z, Sledge D, Levin ED. Buspirone, chlordiazepoxide and diazepam effects in a zebrafish model of anxiety. Pharmacol Biochem Behav 2009;94:75-80.&#13;
143. Best JD, Alderton WK. Zebrafish: An in vivo model for the study of neurological diseases. Neuropsychiatr Dis Treat 2008;4:567-76.&#13;
144. Kalueff AV, Stewart AM, Gerlai R. Zebrafish as an emerging model for studying complex brain disorders. Trends Pharmacol Sci 2014;35:63-75.&#13;
145. Stewart AM, Braubach O, Spitsbergen J, Gerlai R, Kalueff AV. Zebrafish models for translational neuroscience research: From tank to bedside. Trends Neurosci 2014;37:264-78.&#13;
146. Piato and;Acirc;L, Capiotti KM, Tamborski AR, Oses JP, Barcellos LJ, Bogo MR, et al. Unpredictable chronic stress model in zebrafish (Danio rerio): Behavioral and physiological responses. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:561-7.&#13;
147. Marcon M, Herrmann AP, Mocelin R, Rambo CL, Koakoski G, Abreu MS, et al. Prevention of unpredictable Devi, et al.: Chronic unpredictable stress and its pathology Pharmaspire | Vol. 14 | No. 1 | 2022 40 chronic stress-related phenomena in zebrafish exposed to bromazepam, fluoxetine and nortriptyline. Psychopharmacology (Berl) 2016;233:3815-24.&#13;
148. Kwong RW, Perry SF. Cortisol regulates epithelial permeability and sodium losses in zebrafish exposed to&#13;
acidic water. J Endocrinol 2013;217:253-64.&#13;
149.Lyche JL, Nourizadeh-Lillabadi R, Almaas C, Stavik B, Berg V, Skand;aring;re JU, et al. Natural mixtures of persistent organic pollutants (POP) increase weight gain, advance puberty, and induce changes in gene expression associated with steroid hormones and obesity in female zebrafish. J Toxicol Environ Health A 2010;73:1032-57.&#13;
150. Richetti SK, Rosemberg DB, Ventura-Lima J, Monserrat JM, Bogo MR, Bonan CD. Acetylcholinesterase activity and antioxidant capacity of zebrafish brain is altered by heavy metal exposure. Neurotoxicology 2011;32:116-22.&#13;
151. Long Y, Li Q, Zhong S, Wang Y, Cui Z. Molecular characterization and functions of zebrafish ABCC2 in cellular efflux of heavy metals. Comp Biochem Physiol C Toxicol Pharmacol 2011;153:381-91.</References>
      </References>
    </Journal>
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