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The Effect of Sericin on the Cognitive Impairment, Depression, and Anxiety Caused by Learned Helplessness in Male Mice

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Abstract

Learned helplessness (LH) induces cognitive and emotional abnormalities via alteration of synaptic and apoptotic markers in the hippocampus. Given the sericin’s neuroprotective effects on different experimental models, this study aimed to address whether sericin is able to reduce LH-induced behavioral and molecular changes in the mouse model. Sixty male mice (3 months old) were randomly divided into control, normal saline (NS), and/or different doses of sericin (Ser [100, 200, and 300 mg/kg]) for 21 days. Accordingly, the animals in NS and sericin-treated groups were subjected to 1 day learned helplessness protocol. Behavioral deficits were evaluated and alterations in both synaptic and apoptotic factors were evaluated in the hippocampus. Induction of LH was associated with behavioral changes (depression and cognitive impairment). On the other hand, the administration of sericin effectively normalized these deficits. At molecular levels, sericin increased the levels of synaptophysin, synapsin-1, and PSD-95, and decreased apoptosis in the hippocampus. Although the exact mechanisms underlying the neuroprotective effects of sericin are not fully understood, our results showed that this effect mediated via modulation of the synaptic and apoptotic proteins in the hippocampus of LH-subjected mice.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  • Anisman H, Merali Z (2001) Rodent models of depression: learned helplessness induced in mice. Curr Prot Neurosci 1(8):10–15

    Google Scholar 

  • Aramwit P, Keongamaroon O, Siritientong T, Bang N, Supasyndh O (2012) Sericin cream reduces pruritus in hemodialysis patients: a randomized, double-blind, placebo-controlled experimental study. BMC Nephrol 1:1–11

    Google Scholar 

  • Bartolomucci A, Pederzani T, Sacerdote P, Panerai AE, Parmigiani S, Palanza P (2004) Behavioral and physiological characterization of male mice under chronic psychosocial stress. Psychoneuroendocrinol 7:899–910

    Article  Google Scholar 

  • Bessa J, Ferreira D, Melo I, Marques F, Cerqueira JJ, Palha JA, Almeida O, Sousa N (2009) The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling. Mol Psychiatry 8:764–773

    Article  CAS  Google Scholar 

  • Chen Z, He Y, Song C, Dong Z, Su Z, Xue J (2012) Sericin can reduce hippocampal neuronal apoptosis by activating the Akt signal transduction pathway in a rat model of diabetes mellitus. Neural Reg Res 3:197

    Google Scholar 

  • Cheng D, Hoogenraad CC, Rush J, Ramm E, Schlager MA, Duong DM, Xu P, Wijayawardana SR, Hanfelt J, Nakagawa T (2006) Relative and absolute quantification of postsynaptic density proteome isolated from rat forebrain and cerebellum. Mol Cell Proteomics 6:1158–1170

    Article  CAS  Google Scholar 

  • Chourbaji S, Zacher C, Sanchis-Segura C, Dormann C, Vollmayr B, Gass P (2005) Learned helplessness: validity and reliability of depressive-like states in mice. Brain Res Prot 1–3:70–78

    Article  Google Scholar 

  • Coley AA, Gao W-J (2018) PSD95: a synaptic protein implicated in schizophrenia or autism?. Prog Neuropsychopharmacol Biol Psychiatry 82:187–194

    Article  CAS  PubMed  Google Scholar 

  • Danial NN, Korsmeyer SJ (2004) Cell death: critical control points. Cell 2:205–219

    Article  Google Scholar 

  • De Kloet ER, Joëls M, Holsboer F (2005) Stress and the brain: from adaptation to disease. Nat Rev Neurosci 6:463–475

    Article  PubMed  CAS  Google Scholar 

  • Denninger JK, Smith BM, Kirby ED (2018) Novel object recognition and object location behavioral testing in mice on a budget. J vis Exp 20:141

    Google Scholar 

  • Eastwood SL, Harrison PJ (2001) Synaptic pathology in the anterior cingulate cortex in schizophrenia and mood disorders. A review and a Western blot study of synaptophysin, GAP-43 and the complexins. Brain Res Bull 5:569–578

    Article  Google Scholar 

  • Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 4:495–516

    Article  CAS  Google Scholar 

  • Fan C, Song Q, Wang P, Li Y, Yang M, Yu SY (2018) Neuroprotective effects of ginsenoside-Rg1 against depression-like behaviors via suppressing glial activation, synaptic deficits, and neuronal apoptosis in rats. Front Immunol 9:2889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fang ZH, Lee CH, Seo MK, Cho H, Lee JG, Lee BJ, Park SW, Kim YH (2013) Effect of treadmill exercise on the BDNF-mediated pathway in the hippocampus of stressed rats. Neurosci Res 4:187–194

    Article  CAS  Google Scholar 

  • Fekri K, Fereshteh J M S S-E, Alireza F, Nayebi M (2021) Coumestrol alleviates oxidative stress, apoptosis and cognitive impairments through hippocampal estrogen receptor-beta in male mouse model of chronic restraint stress. Pharm Sci. In Press

  • Fernández E, Collins MO, Frank RA, Zhu F, Kopanitsa MV, Nithianantharajah J, Lemprière SA, Fricker D, Elsegood KA, McLaughlin CL (2017) Arc requires PSD95 for assembly into postsynaptic complexes involved with neural dysfunction and intelligence. Cell Rep 3:679–691

    Article  CAS  Google Scholar 

  • Feyissa AM, Woolverton WL, Miguel-Hidalgo JJ, Wang Z, Kyle PB, Hasler G, Stockmeier CA, Iyo AH, Karolewicz B (2010) Elevated level of metabotropic glutamate receptor 2/3 in the prefrontal cortex in major depression. Prog Neuropsychopharmacol Biol Psychiatry 2:279–283

    Article  CAS  Google Scholar 

  • Fromer M, Pocklington AJ, Kavanagh DH, Williams HJ, Dwyer S, Gormley P, Georgieva L, Rees E, Palta P, Ruderfer DM (2014) De novo mutations in schizophrenia implicate synaptic networks. Nature 7487:179–184

    Article  CAS  Google Scholar 

  • Fuchs Y, Steller H (2011) Programmed cell death in animal development and disease. Cell 4:742–758

    Article  CAS  Google Scholar 

  • Gould E, Tanapat P, McEwen BS, Flügge G, Fuchs E (1998) Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc Natl Acad Sci U S A 6:3168–3171

    Article  Google Scholar 

  • Han K, Kim E (2008) Synaptic adhesion molecules and PSD-95. Prog Neurobiol 3:263–283

    Article  CAS  Google Scholar 

  • Hasler G, Drevets W, Manji H, Charney DS (2004) Discovering Endophenotypes for Major Depression Neuropsychopharmacol 29:1765–1781

    CAS  Google Scholar 

  • Hidayat R, Saleh MI, Parisa N (2020) Neuronal cell death induces depressive disorder in rats depression-like behaviors caused by chronic stress. Scientia Psychiatrica 2:16–24

    Article  Google Scholar 

  • Hsiao YH, Hung HC, Chen SH, Gean PW (2014) Social interaction rescues memory deficit in an animal model of Alzheimer’s disease by increasing BDNF-dependent hippocampal neurogenesis. J Neurosci 49:16207–16219

    Article  CAS  Google Scholar 

  • Hunsberger JG, Machado-Vieira R, Austin DR, Zarate C, Chuang D-M, Chen G, Reed JC, Manji HK (2011) Bax inhibitor 1, a modulator of calcium homeostasis, confers affective resilience. Brain Res 1403:19–27

  • Iwata M, Shirayama Y, Ishida H, Kawahara R (2006) Hippocampal synapsin I, growth-associated protein-43, and microtubule-associated protein-2 immunoreactivity in learned helplessness rats and antidepressant-treated rats. Neurosci 3:1301–1313

    Article  CAS  Google Scholar 

  • Jackson RL, Maier SF, Rapaport PM (1978) Exposure to inescapable shock produces both activity and associative deficits in the rat. Learn Motiv 1:69–98

    Article  Google Scholar 

  • Jianhua F, Wei W, Xiaomei L, Shao-Hui W (2017) Chronic social defeat stress leads to changes of behaviour and memory-associated proteins of young mice. Behav Brain Res 316:136–144

  • Joëls M, Karst H, Alfarez D, Heine VM, Qin Y, Riel EV, Verkuyl M, Lucassen PJ, Krugers HJ (2004) Effects of chronic stress on structure and cell function in rat hippocampus and hypothalamus. Stress 4:221–231

    Article  CAS  Google Scholar 

  • Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS (2003) The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 23:3095–3105

    Article  Google Scholar 

  • Kessler RC, Bromet EJ (2013) The epidemiology of depression across cultures. Ann Rev Pub Health 34:119–138

  • Kim H-W, Rapoport SI, Rao JS (2010) Altered expression of apoptotic factors and synaptic markers in postmortem brain from bipolar disorder patients. Neurobiol Dis 3:596–603

    Article  CAS  Google Scholar 

  • Kim Y, Perova Z, Mirrione MM, Pradhan K, Henn FA, Shea S, Osten P, Li B (2016) Whole-brain mapping of neuronal activity in the learned helplessness model of depression. Front Neural Cir 10:3

    Google Scholar 

  • Kosten TA, Galloway MP, Duman RS, Russell DS, D’sa C (2008) Repeated unpredictable stress and antidepressants differentially regulate expression of the bcl-2 family of apoptotic genes in rat cortical, hippocampal, and limbic brain structures. Neuropsychopharmacol 7:1545–1558

    Article  CAS  Google Scholar 

  • Kowaltowski AJ, Fenton RG, Fiskum G (2004) Bcl-2 family proteins regulate mitochondrial reactive oxygen production and protect against oxidative stress. Free Radical Biol and Med 11:1845–1853

    Article  CAS  Google Scholar 

  • Kubera M, Obuchowicz E, Goehler L, Brzeszcz J, Maes M (2011) In animal models, psychosocial stress-induced (neuro) inflammation, apoptosis and reduced neurogenesis are associated to the onset of depression. Prog Neuropsychopharmacol Biol Psychiatry 3:744–759

    Article  CAS  Google Scholar 

  • Kunz RI, Brancalhão RMC, Ribeiro LDFC, Natali MRM (2016) Silkworm sericin: properties and biomedical applications. BioMed Res Internat 2016:1–12

  • Landgraf D, Long J, Der-Avakian A, Streets M, Welsh DK (2015) Dissociation of learned helplessness and fear conditioning in mice: a mouse model of depression. PloS One 4:e0125892

    Article  CAS  Google Scholar 

  • Liu Y, Ma S, Qu R (2010) SCLM, total saponins extracted from Chaihu-jia-longgu-muli-tang, reduces chronic mild stress-induced apoptosis in the hippocampus in mice. Pharmaceut Biol 8:840–848

    Article  CAS  Google Scholar 

  • Lledo P-M, Saghatelyan A (2005) Integrating new neurons into the adult olfactory bulb: joining the network, life–death decisions, and the effects of sensory experience. Trends Neurosci 5:248–254

    Article  CAS  Google Scholar 

  • Lucassen PJ, Heine VM, Muller MB, van der Beek EM, Wiegant VM, Ron De Kloet E, Joels M, Fuchs E, Swaab DF, Czeh B (2006) Stress, depression and hippocampal apoptosis. CNS Neurol Disord Drug Targets 5:531–546

    Article  PubMed  Google Scholar 

  • Luo J, Zhang L, Ning N, Jiang H, Yu SY (2013) Neotrofin reverses the effects of chronic unpredictable mild stress on behavior via regulating BDNF, PSD-95 and synaptophysin expression in rat. Behav Brain Res 253:48–53

  • Mahmoudi J, Farhoudi M, Talebi M, Sabermarouf B, Sadigh-Eteghad S (2015) Antidepressant-like effect of modafinil in mice: evidence for the involvement of the dopaminergic neurotransmission. Pharmacol Rep 3:478–484

    Article  CAS  Google Scholar 

  • Mahmoudi J, Hosseini L, Sadigh-Eteghad S, Farajdokht F, Vatandoust SM, Ziaee M (2021) Sericin alleviates thermal stress induced anxiety-like behavior and cognitive impairment through regulation of oxidative stress, apoptosis, and heat-shock protein-70 in the hippocampus. Neurochem Res 9:2307–2316

    Article  CAS  Google Scholar 

  • Maier SF (1990) Role of fear in mediating shuttle escape learning deficit produced by inescapable shock. Journal of Experimental Psychology: Animal BehavProces 2:137

    Google Scholar 

  • Marttinen M, Kurkinen KM, Soininen H, Haapasalo A, Hiltunen M (2015) Synaptic dysfunction and septin protein family members in neurodegenerative diseases. Mol Neurodeg 1:1–12

    Google Scholar 

  • Masliah E, Terry R (1993) The role of synaptic proteins in the pathogenesis of disorders of the central nervous system. Brain Pathol 1:77–85

    Article  Google Scholar 

  • Mohammadi AB, Torbati M, Farajdokht F, Sadigh-Eteghad S, Fazljou SMB, Vatandoust SM, Golzari SE, Mahmoudi J (2019) Sericin alleviates restraint stress induced depressive-and anxiety-like behaviors via modulation of oxidative stress, neuroinflammation and apoptosis in the prefrontal cortex and hippocampus. Brain Res 1715:47–56

  • Morris MC, Compas BE, Garber J (2012) Relations among posttraumatic stress disorder, comorbid major depression, and HPA function: a systematic review and meta-analysis. Clinical Psychol Rev 4:301–315

    Article  Google Scholar 

  • Murray CJ, Lopez AD, Organization WH (1996) The global burden of disease: a comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020: summary. World Health Organization

    Google Scholar 

  • Park HJ, Kim SK, Kang WS, Chung JH, Kim JW (2014) Increased activation of synapsin 1 and mitogen activated protein kinases/extracellular signal regulated kinase in the amygdala of maternal separation rats. CNS Neurosci Therap 2:172–181

    Article  CAS  Google Scholar 

  • Peera K, Yellamma K (2015) Sericin as a cholinergic modulator in alzheimer’s disease induced rat. Int J Pharm Pharm Sci 7(4):108–112

  • Pizarro JM, Lumley LA, Medina W, Robison CL, Chang WE, Alagappan A, Bah MJ, Dawood MY, Shah JD, Mark B (2004) Acute social defeat reduces neurotrophin expression in brain cortical and subcortical areas in mice. Brain Res 1–2:10–20

    Article  CAS  Google Scholar 

  • Portt L, Norman G, Clapp C, Greenwood M, Greenwood MT (2011) Anti-apoptosis and cell survival: a review. Biochim Biophys Acta (BBA)-Mol Cell Rese 1:238–259

    Article  CAS  Google Scholar 

  • Raju DV, Ahern TH, Shah DJ, Wright TM, Standaert DG, Hall RA, Smith Y (2008) Differential synaptic plasticity of the corticostriatal and thalamostriatal systems in an MPTP-treated monkey model of parkinsonism. Europ J Neurosci 7:1647–1658

    Article  Google Scholar 

  • Rapp S, Baader M, Hu M, Jennen-Steinmetz C, Henn F, Thome J (2004) Differential regulation of synaptic vesicle proteins by antidepressant drugs. Pharmacog J 2:110–113

    Article  CAS  Google Scholar 

  • Raps CS, Reinhard KE, Seligman ME (1980) Reversal of cognitive and affective deficits associated with depression and learned helplessness by mood elevation in patients. J Abnormal Psychol 3:342

    Article  Google Scholar 

  • Roth S (1980) A revised model of learned helplessness in humans 1. J Personal 1:103–133

    Article  Google Scholar 

  • Salehpour F, Mahmoudi J, Farajdokht F, Eyvazzadeh N (2018) Noise stress impairs social interaction in adult male mice: role of oxidative stress and neuroendocrine markers. Crescent J Med Biol Sci 4:272–278

    Google Scholar 

  • Salehpour F, Mahmoudi J, Sadigh-Eteghad S, Cassano P (2019) Photobiomodulation for depression in animal models. Elsevier, Photobiomod Brain, pp 189–205

    Google Scholar 

  • Sapolsky RM (2000) Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 10:925–935

    Article  Google Scholar 

  • Sato K, Morimoto K, Suemaru S, Sato T, Yamada N (2000) Increased synapsin I immunoreactivity during long-term potentiation in rat hippocampus. Brain Res 1–2:219–222

    Article  Google Scholar 

  • Schmidt-Hieber C, Jonas P, Bischofberger J (2004) Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature 6988:184–187

    Article  CAS  Google Scholar 

  • Seese RR, Chen LY, Cox CD, Schulz D, Babayan AH, Bunney WE, Henn FA, Gall CM, Lynch G (2013) Synaptic abnormalities in the infralimbic cortex of a model of congenital depression. J Neurosci 33:13441–13448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seyedaghamiri F, Farajdokht F, Vatandoust SM, Mahmoudi J, Khabbaz A, Sadigh-Eteghad S (2021) Sericin modulates learning and memory behaviors by tuning of antioxidant, inflammatory, and apoptotic markers in the hippocampus of aged mice. Mol Biol Rep 2:1371–1382

    Article  CAS  Google Scholar 

  • Short KR, Maier SF (1993) Stressor controllability, social interaction, and benzodiazepine systems. Pharmacol Biochem Behav 4:827–835

    Article  Google Scholar 

  • Silva R, Mesquita A, Bessa J, Sousa JC, Sotiropoulos I, Leão P, Almeida OF, Sousa N (2008) Lithium blocks stress-induced changes in depressive-like behavior and hippocampal cell fate: the role of glycogen-synthase-kinase-3β. Neurosci 3:656–669

    Article  CAS  Google Scholar 

  • Smalheiser NR, Zhang H, Dwivedi Y (2014) Enoxacin elevates microRNA levels in rat frontal cortex and prevents learned helplessness. Front Psych 6(5):1-7

  • Smith MA, Makino S, Kvetnansky R, Post RM (1995) Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci 3:1768–1777

    Article  Google Scholar 

  • Spiwoks-Becker I, Vollrath L, Seeliger M, Jaissle G, Eshkind L, Leube R (2001) Synaptic vesicle alterations in rod photoreceptors of synaptophysin-deficient mice. Neurosci 1:127–142

    Article  Google Scholar 

  • Su C-L, Su C-W, Hsiao Y-H, Gean P-W (2016) Epigenetic regulation of BDNF in the learned helplessness-induced animal model of depression. J Psych Res 76:101–110

  • Sullivan DR, Liu X, Corwin DS, Verceles AC, McCurdy MT, Pate DA, Davis JM, Netzer G (2012) Learned helplessness among families and surrogate decision-makers of patients admitted to medical, surgical, and trauma ICUs. Chest 6:1440–1446

    Article  Google Scholar 

  • Suri D, Vaidya V (2013) Glucocorticoid regulation of brain-derived neurotrophic factor: relevance to hippocampal structural and functional plasticity. Neurosci 239:196–213

  • Tait SW, Green DR (2010) Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol 9:621–632

    Article  CAS  Google Scholar 

  • Tarsa L, Goda Y (2002) Synaptophysin regulates activity-dependent synapse formation in cultured hippocampal neurons. Proc Natl Acad Sci U S A 2:1012–1016

    Article  CAS  Google Scholar 

  • Tsigos C, Chrousos GP (2002) Hypothalamic–pituitary–adrenal axis, neuroendocrine factors and stress. J Psychosomatic Res 4:865–871

    Article  Google Scholar 

  • Wang J, Xu S, Chen X, Wang L, Li J, Li G, Zhang B (2020) Antidepressant effect of EGCG through the inhibition of hippocampal neuroinflammation in chronic unpredictable mild stress-induced depression rat model. J Funct Foods 104106

  • Wang M, Perova Z, Arenkiel BR, Li B (2014) Synaptic modifications in the medial prefrontal cortex in susceptibility and resilience to stress. J Neurosci 22:7485–7492

    Article  CAS  Google Scholar 

  • Wang PS, Simon G, Kessler RC (2003) The economic burden of depression and the costeffectiveness of treatment. Int J Methods Psychiatr Res 1:22–33

    Article  Google Scholar 

  • Weiss J, Simson PG (1986) Depression in an animal model: focus on the locus coeruleus. Antidepressants Recept Func 123:191–215

    CAS  Google Scholar 

  • Wingenfeld K, Wolf OT (2014) Stress, memory, and the hippocampus. Hippocam Clin Neurosci 34:109–120

    Article  Google Scholar 

  • Wortman CB, Brehm JW (1975) Responses to uncontrollable outcomes: an integration of reactance theory and the learned helplessness model. Adv Exp Soc Psychol 8:277–336

    Article  Google Scholar 

  • Yellamma K (2014) Silk protein, sericin as a cognitive enhancer in Alzheimer’s disease. J Alzheimers Dis Parkinsonism 163(2161–0460):1000163

    Google Scholar 

  • Yuan J, Yankner BA (2000) Apoptosis in the nervous system. Nature 6805:802–809

    Article  Google Scholar 

  • Zhang L, Luo J, Zhang M, Yao W, Ma X, Yu SY (2014) Effects of curcumin on chronic, unpredictable, mild, stress-induced depressive-like behaviour and structural plasticity in the lateral amygdala of rats. Inter J Neuropsychopharmacol 5:793–806

    Article  CAS  Google Scholar 

  • Zhang Y-Q (2002) Applications of natural silk protein sericin in biomaterials. Biotech Adv 2:91–100

    Article  Google Scholar 

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Acknowledgements

The authors would like thanks to Neuroscience Research Center, Baqiyatallah University of Medical Sciences, and Neurosciences Research Center of Tabriz University of Medical Sciences for their technical supports.

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    Seyed Mehdi Vatandoust & Gholam Hossein Meftahi

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Seyed Mehdi Vatandoust and Gholam Hossein Meftahi performed the experiments, analyzed interpreted the data, designed the experiments and edited the paper. All authors read and approved the final manuscript.

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Correspondence to Gholam Hossein Meftahi.

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Vatandoust, S.M., Meftahi, G.H. The Effect of Sericin on the Cognitive Impairment, Depression, and Anxiety Caused by Learned Helplessness in Male Mice. J Mol Neurosci 72, 963–974 (2022). https://doi.org/10.1007/s12031-022-01982-3

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