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.
journal_name
Prog Neuropsychopharmacol Biol Psychiatryauthors
Li Y,Li S,Yan J,Wang D,Yin R,Zhao L,Zhu Y,Zhu Xdoi
10.1016/j.pnpbp.2015.09.004subject
Has Abstractpub_date
2016-02-04 00:00:00pages
96-103eissn
0278-5846issn
1878-4216pii
S0278-5846(15)30040-3journal_volume
65pub_type
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