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Current Neurovascular Research

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ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

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Research Article

Hippocampal miR-124 Participates in the Pathogenesis of Depression via Regulating the Expression of BDNF in a Chronic Social Defeat Stress Model of Depression

Author(s): Lin-Sheng Shi*, Chun-Hui Ji, Wen-Qian Tang, Yue Liu, Wei Zhang and Wei Guan

Volume 19, Issue 2, 2022

Published on: 22 July, 2022

Page: [210 - 218] Pages: 9

DOI: 10.2174/1567202619666220713105306

Price: $65

Abstract

Objective: As one of the most prevalent psychiatric disorders, the exact pathogenesis of depression remains elusive. Therefore, there is an urgent need to identify novel antidepressants for effective treatment. MicroRNA-124 (miR-124), the most abundant miRNA in brain tissue, plays a key effect on adult neurogenesis and neuronal differentiation. However, the mechanism of miR-124 in depression has not been clarified so far. The aim of this study is to provide broad insight into the mechanisms underlying depression.

Methods: In the study, we used the forced swim test (FST), the tail suspension test (TST), and a Chronic Social Defeat Stress (CSDS) mice model of depression. Quantitative real-time reverse transcription PCR (qRT-PCR), western blotting, immunofluorescence and virus-mediated gene transfer were used together. The level of plasma corticosterone in mice was analyzed by Enzyme Linked Immunosorbent Assay (ELISA).

Results: It was found that CSDS robustly increased the level of miR-124 in the hippocampus. Genetic knockdown of hippocampal miR-124 produced significant antidepressant-like effects in the CSDS model of depression. Furthermore, AAV-siR-124-EGFP treatment increased the level of plasma corticosterone in CSDS-induced mice. Moreover, it was found that the antidepressant-like effects induced by miR-124 inhibition required the hippocampal BDNF-TrkB system.

Conclusion: Hippocampal miR-124 participated in the pathogenesis of depression by regulating BDNF biosynthesis and was a feasible antidepressant target.

Keywords: Antidepressant, brain-derived neurotrophic factor, chronic social defeat stress, depression, hippocampal neurogenesis, miR-124.

« Previous Next »
[1]
Xu J, Zheng Y, Wang L, et al. miR-124: A promising therapeutic target for central nervous system injuries and diseases. Cell Mol Neurobiol 2021. Epub ahead of print
[http://dx.doi.org/10.1007/s10571-021-01091-6] [PMID: 33886036]
[2]
Greenberg PE, Fournier AA, Sisitsky T, Pike CT, Kessler RC. The economic burden of adults with major depressive disorder in the United States (2005 and 2010). J Clin Psychiatry 2015; 76(2): 155-62.
[http://dx.doi.org/10.4088/JCP.14m09298] [PMID: 25742202]
[3]
Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron 2002; 34(1): 13-25.
[http://dx.doi.org/10.1016/S0896-6273(02)00653-0] [PMID: 11931738]
[4]
Krishnan V, Nestler EJ. The molecular neurobiology of depression. Nature 2008; 455(7215): 894-902.
[http://dx.doi.org/10.1038/nature07455] [PMID: 18923511]
[5]
Dean J, Keshavan M. The neurobiology of depression: An integrated view. Asian J Psychiatr 2017; 27: 101-11.
[http://dx.doi.org/10.1016/j.ajp.2017.01.025] [PMID: 28558878]
[6]
Björkholm C, Monteggia LM. BDNF - a key transducer of antidepressant effects. Neuropharmacology 2016; 102: 72-9.
[http://dx.doi.org/10.1016/j.neuropharm.2015.10.034] [PMID: 26519901]
[7]
Dunham JS, Deakin JF, Miyajima F, Payton A, Toro CT. Expression of hippocampal brain-derived neurotrophic factor and its receptors in Stanley consortium brains. J Psychiatr Res 2009; 43(14): 1175-84.
[http://dx.doi.org/10.1016/j.jpsychires.2009.03.008] [PMID: 19376528]
[8]
Qi XR, Zhao J, Liu J, Fang H, Swaab DF, Zhou JN. Abnormal retinoid and TrkB signaling in the prefrontal cortex in mood disorders. Cereb Cortex 2015; 25(1): 75-83.
[http://dx.doi.org/10.1093/cercor/bht203] [PMID: 23960204]
[9]
Tripp A, Oh H, Guilloux JP, Martinowich K, Lewis DA, Sibille E. Brain-derived neurotrophic factor signaling and subgenual anterior cingulate cortex dysfunction in major depressive disorder. Am J Psychiatry 2012; 169(11): 1194-202.
[http://dx.doi.org/10.1176/appi.ajp.2012.12020248] [PMID: 23128924]
[10]
Bartel DP. MicroRNAs: Target recognition and regulatory functions. Cell 2009; 136(2): 215-33.
[http://dx.doi.org/10.1016/j.cell.2009.01.002] [PMID: 19167326]
[11]
Huntzinger E, Izaurralde E. Gene silencing by microRNAs: Contributions of translational repression and mRNA decay. Nat Rev Genet 2011; 12(2): 99-110.
[http://dx.doi.org/10.1038/nrg2936] [PMID: 21245828]
[12]
Åkerblom M, Jakobsson J. MicroRNAs as neuronal fate determinants. Neuroscientist 2014; 20(3): 235-42.
[http://dx.doi.org/10.1177/1073858413497265] [PMID: 23877999]
[13]
Roy B, Dunbar M, Shelton RC, Dwivedi Y. Identification of microRNA-124-3p as a putative epigenetic signature of major depressive disorder. Neuropsychopharmacology 2017; 42(4): 864-75.
[http://dx.doi.org/10.1038/npp.2016.175] [PMID: 27577603]
[14]
Dwivedi Y, Roy B, Lugli G, Rizavi H, Zhang H, Smalheiser NR. Chronic corticosterone-mediated dysregulation of microRNA network in prefrontal cortex of rats: Relevance to depression pathophysiology. Transl Psychiatry 2015; 5(11): e682.
[http://dx.doi.org/10.1038/tp.2015.175] [PMID: 26575223]
[15]
Bahi A, Chandrasekar V, Dreyer JL. Selective lentiviral-mediated suppression of microRNA124a in the hippocampus evokes antidepressants-like effects in rats. Psychoneuroendocrinology 2014; 46: 78-87.
[http://dx.doi.org/10.1016/j.psyneuen.2014.04.009] [PMID: 24882160]
[16]
Guan W, Xu DW, Ji CH, et al. Hippocampal miR-206-3p participates in the pathogenesis of depression via regulating the expression of BDNF. Pharmacol Res 2021; 174: 105932.
[http://dx.doi.org/10.1016/j.phrs.2021.105932] [PMID: 34628001]
[17]
Kosuge A, Kunisawa K, Arai S, et al. Heat-sterilized bifidobacterium breve prevents depression-like behavior and interleukin-1β expression in mice exposed to chronic social defeat stress. Brain Behav Immun 2021; 96: 200-11.
[http://dx.doi.org/10.1016/j.bbi.2021.05.028] [PMID: 34062230]
[18]
Ren Y, Wang JL, Zhang X, et al. Antidepressant-like effects of ginsenoside Rg2 in a chronic mild stress model of depression. Brain Res Bull 2017; 134: 211-9.
[http://dx.doi.org/10.1016/j.brainresbull.2017.08.009] [PMID: 28842305]
[19]
Xu D, Sun Y, Wang C, et al. Hippocampal mTOR signaling is required for the antidepressant effects of paroxetine. Neuropharmacology 2018; 128: 181-95.
[http://dx.doi.org/10.1016/j.neuropharm.2017.10.008] [PMID: 29030165]
[20]
Jiang B, Huang C, Zhu Q, Tong LJ, Zhang W. WY14643 produces anti-depressant-like effects in mice via the BDNF signaling pathway. Psychopharmacology (Berl) 2015; 232(9): 1629-42.
[http://dx.doi.org/10.1007/s00213-014-3802-0] [PMID: 25388293]
[21]
Jiang B, Huang C, Chen XF, Tong LJ, Zhang W. Tetramethylpyrazine produces antidepressant-like effects in mice through promotion of BDNF signaling pathway. Int J Neuropsychopharmacol 2015; 18(8): pyv010.
[http://dx.doi.org/10.1093/ijnp/pyv010] [PMID: 25618406]
[22]
Deng X, Ji Z, Xu B, et al. Suppressing the Na+/H+ exchanger 1: A new sight to treat depression. Cell Death Dis 2019; 10(5): 370.
[http://dx.doi.org/10.1038/s41419-019-1602-5] [PMID: 31068571]
[23]
Krishnan V, Han MH, Graham DL, et al. Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell 2007; 131(2): 391-404.
[http://dx.doi.org/10.1016/j.cell.2007.09.018] [PMID: 17956738]
[24]
Zhao H, Mohamed NE, Chan SJ, et al. Absence of stress response in dorsal raphe nucleus in modulator of apoptosis 1-deficient mice. Mol Neurobiol 2019; 56(3): 2185-201.
[http://dx.doi.org/10.1007/s12035-018-1205-7] [PMID: 30003515]
[25]
Stepanichev MY, Tishkina AO, Novikova MR, et al. Anhedonia but not passive floating is an indicator of depressive-like behavior in two chronic stress paradigms. Acta Neurobiol Exp (Warsz) 2016; 76(4): 324-33.
[http://dx.doi.org/10.21307/ane-2017-031] [PMID: 28094823]
[26]
Sebastian V, Estil JB, Chen D, Schrott LM, Serrano PA. Acute physiological stress promotes clustering of synaptic markers and alters spine morphology in the hippocampus. PLoS One 2013; 8(10): e79077.
[http://dx.doi.org/10.1371/journal.pone.0079077] [PMID: 24205365]
[27]
Guan W, Cheng F, Wu H, et al. GATA binding protein 3 is correlated with leptin regulation of PPARγ1 in hepatic stellate cells. J Cell Mol Med 2017; 21(3): 568-78.
[http://dx.doi.org/10.1111/jcmm.13002] [PMID: 27709831]
[28]
Guan W, Gu JH, Ji CH, et al. Xanthoceraside administration produces significant antidepressant effects in mice through activation of the hippocampal BDNF signaling pathway. Neurosci Lett 2021; 757: 135994.
[http://dx.doi.org/10.1016/j.neulet.2021.135994] [PMID: 34058291]
[29]
Hashimoto K. Molecular mechanisms of the rapid-acting and long-lasting antidepressant actions of (R)-ketamine. Biochem Pharmacol 2020; 177: 113935.
[http://dx.doi.org/10.1016/j.bcp.2020.113935] [PMID: 32224141]
[30]
Wan Y, Liu Y, Wang X, et al. Identification of differential microRNAs in cerebrospinal fluid and serum of patients with major depressive disorder. PLoS One 2015; 10(3): e0121975.
[http://dx.doi.org/10.1371/journal.pone.0121975] [PMID: 25763923]
[31]
Martins M, Rosa A, Guedes LC, et al. Convergence of miRNA expression profiling, α-synuclein interacton and GWAS in Parkinson’s disease. PLoS One 2011; 6(10): e25443.
[http://dx.doi.org/10.1371/journal.pone.0025443] [PMID: 22003392]
[32]
Saraiva C, Esteves M, Bernardino L. MicroRNA: Basic concepts and implications for regeneration and repair of neurodegenerative diseases. Biochem Pharmacol 2017; 141: 118-31.
[http://dx.doi.org/10.1016/j.bcp.2017.07.008] [PMID: 28709951]
[33]
Su W, Aloi MS, Garden GA. MicroRNAs mediating CNS inflammation: Small regulators with powerful potential. Brain Behav Immun 2016; 52: 1-8.
[http://dx.doi.org/10.1016/j.bbi.2015.07.003] [PMID: 26148445]
[34]
Yoshino Y, Roy B, Dwivedi Y. Corticosterone-mediated regulation and functions of miR-218-5p in rat brain. Sci Rep 2022; 12(1): 194.
[http://dx.doi.org/10.1038/s41598-021-03863-y] [PMID: 34996981]
[35]
Clark CT, Sit DK, Zumpf KB, et al. A comparison of symptoms of bipolar and unipolar depression in postpartum women. J Affect Disord 2022; 303: 82-90.
[http://dx.doi.org/10.1016/j.jad.2022.01.064] [PMID: 35041868]
[36]
Lin L, Herselman MF, Zhou XF, Bobrovskaya L. Effects of corticosterone on BDNF expression and mood behaviours in mice. Physiol Behav 2022; 247: 113721.
[http://dx.doi.org/10.1016/j.physbeh.2022.113721] [PMID: 35074305]
[37]
Zhang C, Zhu L, Lu S, et al. The antidepressant-like effect of formononetin on chronic corticosterone-treated mice. Brain Res 2022; 1783: 147844.
[http://dx.doi.org/10.1016/j.brainres.2022.147844] [PMID: 35218705]
[38]
Metzger M, Souza R, Lima LB, et al. Habenular connections with the dopaminergic and serotonergic system and their role in stress-related psychiatric disorders. Eur J Neurosci 2021; 53(1): 65-88.
[http://dx.doi.org/10.1111/ejn.14647] [PMID: 31833616]
[39]
Higuchi F, Uchida S, Yamagata H, et al. Hippocampal microRNA-124 enhances chronic stress resilience in mice. J Neurosci 2016; 36(27): 7253-67.
[http://dx.doi.org/10.1523/JNEUROSCI.0319-16.2016] [PMID: 27383599]
[40]
Wang Q, Zhao G, Yang Z, Liu X, Xie P. Downregulation of microRNA 124 3p suppresses the mTOR signaling pathway by targeting DDIT4 in males with major depressive disorder. Int J Mol Med 2018; 41(1): 493-500.
[PMID: 29115444]
[41]
Rafało-Ulińska A, Brański P, Pałucha-Poniewiera A. Combined administration of (R)-ketamine and the mGlu2/3 receptor antagonist LY341495 induces rapid and sustained effects in the CUMS model of depression via a TrkB/BDNF-dependent mechanism. Pharmaceuticals (Basel) 2022; 15(2): 125.
[http://dx.doi.org/10.3390/ph15020125] [PMID: 35215237]
[42]
Li J, Gao W, Zhao Z, et al. Ginsenoside Rg1 reduced microglial activation and mitochondrial dysfunction to alleviate depression-like behaviour via the GAS5/EZH2/SOCS3/NRF2 axis. Mol Neurobiol 2022; 59(5): 2855-73.
[http://dx.doi.org/10.1007/s12035-022-02740-7] [PMID: 35230663]
[43]
Mendonça IP, Paiva IHR, Duarte-Silva EP, et al. Metformin and fluoxetine improve depressive-like behavior in a murine model of Parkinsońs disease through the modulation of neuroinflammation, neurogenesis and neuroplasticity. Int Immunopharmacol 2022; 102: 108415.
[http://dx.doi.org/10.1016/j.intimp.2021.108415] [PMID: 34890997]

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