Abstract
Background: Venlafaxine has been demonstrated to treat diseases such as social anxiety disorder and depression. Most of antidepressants including venlafaxine have a certain effect, but significant side effects. Therefore, it is necessary for us to research the development of novel antidepressants for effective treatment in practice. MicroRNA-204 (miR-204) is highly expressed in brain tissue, and plays a critical role in the synaptic plasticity of hippocampal neurons in rats. However, the underlying molecular mechanism of miR-204 remains unclear to date, this study aims to offer unique insights into depression and provide a theoretical basis for clinical physicians.
Methods: A chronic social defeat stress (CSDS) was initially adopted for establishing a mice model of depression in this research and depression-like behaviors were evaluated by a series of behavioral experiments including the sucrose preference test (SPT), the tail suspension test (TST), the forced swim test (FST) and the social interaction test (SIT). Quantitative real-time reverse transcription PCR (qRT-PCR) was also conducted to test the expression levels of miR-204 and BDNF in the hippocampus of mice. Finally, gene interference of miR-204-5p was further adopted to test whether miR-204-5p played an effective role in the antidepressant effects of venlafaxine in mice.
Results: Our data implicated that CSDS significantly increased the miR-204-5p but not miR-204-3p levels in the hippocampus of mice. The treatment of venlafaxine obviously relieved depression- like behaviors of CSDS-induced mice. The usage of venlafaxine abolished the increasing effects on the expression of miR-204-5p but up-regulated the BDNF expression level in CSDS-exposured mice. More importantly, we found that genetic overexpression of miR-204-5p decreased the reverse effects of venlafaxine on depressive-like behaviors and genetic knockdown of hippocampal miR-204-5p relieved the depressive-like behaviors and neurogenesis in CSDS-induced mice.
Conclusion: miR-204-5p played an effective role in the antidepressant effects of venlafaxine in CSDS-induced mice.
Keywords: Venlafaxine, miR-204-5p, depression, chronic social defeat stress, brain-derived neurotrophic factor, hippocampal neurogenesis.
[http://dx.doi.org/10.3390/neurolint13030038] [PMID: 34449705]
[http://dx.doi.org/10.1186/s12888-021-03253-8] [PMID: 34011310]
[http://dx.doi.org/10.1016/0014-2999(85)90684-3] [PMID: 2998818]
[http://dx.doi.org/10.1016/j.drudis.2014.08.017] [PMID: 25224017]
[http://dx.doi.org/10.1177/1073858413497265] [PMID: 23877999]
[http://dx.doi.org/10.1038/npp.2016.175] [PMID: 27577603]
[http://dx.doi.org/10.1017/S1461145713000448] [PMID: 23684180]
[http://dx.doi.org/10.1172/JCI148853] [PMID: 34228643]
[http://dx.doi.org/10.1016/j.phrs.2021.105932] [PMID: 34628001]
[http://dx.doi.org/10.2174/1567202617666200319141755] [PMID: 32189593]
[http://dx.doi.org/10.1038/sj.npp.1301571] [PMID: 17882234]
[http://dx.doi.org/10.7499/j.issn.1008-8830.2205140] [PMID: 36544422]
[http://dx.doi.org/10.1016/j.brainresbull.2018.09.002] [PMID: 30236533]
[http://dx.doi.org/10.1034/j.1399-5618.2002.01203.x] [PMID: 12180273]
[PMID: 25197330]
[http://dx.doi.org/10.1016/j.pnpbp.2020.109867] [PMID: 31954757]
[http://dx.doi.org/10.1038/npp.2017.9] [PMID: 28079059]
[http://dx.doi.org/10.1016/j.neulet.2021.135994] [PMID: 34058291]
[http://dx.doi.org/10.1007/s11011-019-00491-4] [PMID: 31630319]
[http://dx.doi.org/10.3390/ijms20071652] [PMID: 30987090]
[http://dx.doi.org/10.1016/j.bbi.2021.05.028] [PMID: 34062230]
[http://dx.doi.org/10.1080/21655979.2021.2009964] [PMID: 34889698]
[http://dx.doi.org/10.1016/j.pbb.2020.173062] [PMID: 33098854]
[http://dx.doi.org/10.1007/s00213-022-06107-7] [PMID: 35294601]
[http://dx.doi.org/10.1007/s12035-018-1205-7] [PMID: 30003515]
[http://dx.doi.org/10.1371/journal.pone.0253009] [PMID: 34101749]
[http://dx.doi.org/10.3390/ijms222111725] [PMID: 34769155]
[http://dx.doi.org/10.1016/j.jad.2020.07.096] [PMID: 32871684]
[http://dx.doi.org/10.1111/ejn.14630] [PMID: 31811669]
[http://dx.doi.org/10.2174/1381612825666190329122852] [PMID: 30931847]
[PMID: 30586536]
[PMID: 34702698]
[http://dx.doi.org/10.3390/ijms222212303] [PMID: 34830186]
[http://dx.doi.org/10.1088/1758-5090/ac23ae] [PMID: 34479220]
[http://dx.doi.org/10.3390/cells10092424] [PMID: 34572073]
[http://dx.doi.org/10.1002/jcb.26599] [PMID: 29236313]
[http://dx.doi.org/10.1016/j.parkreldis.2021.11.020] [PMID: 34839044]
[http://dx.doi.org/10.1186/s12974-021-02299-5] [PMID: 34674723]
[http://dx.doi.org/10.3390/cells8091021] [PMID: 31480771]
[http://dx.doi.org/10.1016/j.jad.2022.01.064] [PMID: 35041868]
[http://dx.doi.org/10.12688/f1000research.14344.1] [PMID: 29899972]
[http://dx.doi.org/10.1038/s41467-020-18167-4] [PMID: 32859919]
[http://dx.doi.org/10.1016/j.cbd.2019.100634] [PMID: 31715506]
[http://dx.doi.org/10.1016/j.cbpc.2020.108918] [PMID: 33141083]
[http://dx.doi.org/10.1038/s41598-020-60133-z] [PMID: 32094409]
[http://dx.doi.org/10.1016/j.jpsychires.2020.02.003] [PMID: 32065946]
[http://dx.doi.org/10.1016/j.biopsych.2020.11.018] [PMID: 33536132]
[http://dx.doi.org/10.1038/s41467-022-29155-1] [PMID: 35318315]
[http://dx.doi.org/10.1001/jamanetworkopen.2021.33090] [PMID: 34779847]