title: miR-182 (microRNA-182) suppression in the hippocampus evokes antidepressant-like effects in rats.
abstract: Depression is a serious and potentially life-threatening mental disorder with unknown etiology. Emerging evidence shows that brain-derived neurotrophic factor (BDNF) and microRNAs (miRNAs) play critical roles in the etiology of depression. However, the molecular mechanisms are not fully understood. Expression of miR-182 and BDNF in the hippocampus were analyzed in a chronic unpredictable mild stress (CUMS) model. Male Wistar rats received bilateral intra-hippocampal infusions of BDNF- and miR-182-expressing (miR-182) or miR-182-silencers (si-miR-182) lentiviral vectors (LV). miR-182 upregulation was correlated with decreased BDNF expression in the hippocampus of a CUMS model. Accordingly, an anti-depressant like effect was observed when LV-BDNF or LV-si-miR-182 was injected into the hippocampus. Moreover, BDNF and its target gene cyclic AMP responsive element binding protein 1 (CREB1) decreased following LV-miR-182 injection and increased upon LV-si-miR-182 injection in rat hippocampus and cultured neuronal cells. In contrast, miR-182 overexpression exacerbated depression-like behaviors and decreased BDNF. Further, luciferase reporter evidence confirmed BDNF was a miR-182 target. Taken together, the current results reveal a potential molecular regulation of miR-182 on BDNF and the pronounced behavioral consequences of this regulation.
authors.affiliation: The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, China; Jiangsu University, Zhenjiang, Jiangsu, 212001, China.
authors.forename: Yuefeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Siyue
authors.initials: S
authors.lastname: Li
authors.affiliation: The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, China.
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Yan
authors.affiliation: The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, China.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Wang
authors.affiliation: The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, China.
authors.forename: Ruigen
authors.initials: R
authors.lastname: Yin
authors.affiliation: The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Jiangsu University, Zhenjiang, Jiangsu, 212001, China; The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, China. Electronic address: jiangdalyf2009@126.com.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002908:Chronic Disease; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003866:Depressive Disorder / Q000378:metabolism* / Q000628:therapy*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006624:Hippocampus / Q000378:metabolism*; D016086:Lentivirus / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000378:metabolism / Q000628:therapy; D035501:Uncertainty
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C508137:Creb1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; C577631:MIRN182 microRNA, rat; D035683:MicroRNAs
keywords: BDNF; Depression; Hippocampus; miR-182