南方医科大学学报2024，Vol.44Issue(7)：1315-1326,12.DOI:10.12122/j.issn.1673-4254.2024.07.11
在抑郁症大鼠模型中MiRNA-103-3p调控Rab10促进神经细胞自噬
MiRNA-103-3p promotes neural cell autophagy by activating Wnt/β-catenin signaling via targeting rab10 in a rat model of depression
摘要
Abstract
Objective To explore the neuroprotective role of Rab10 gene in depression and the mechanism mediating its effect.Methods Forty-eight male SD rats were randomized into a control group and 3 chronic unpredictable mild stress(CUMS)groups(n=12).The rats in the latter 3 groups were subjected to injections of normal saline,an adeno-associated viral(AAV)vector,or a Rab10-overexpressing AAV vector in the lateral ventricle after CUMS modeling.The depressive behavioral changes of the rats were assessed using behavioral tests.The TargetScan database was used to predict the miRNA interacting with Rab10 and the binding sites.The interaction between miRNA-103-3p and Rab10 was investigated using dual-luciferase and radioimmunoprecipitation(RIP)assay.The effect of corticosterone treatment on PC12 cell viability was assessed with CCK-8 assay.In corticosterone-stimulated PC12 cells,the changes in BDNF,CREB,p62,Beclin-1,Wnt3a,Gsk3β,phosphorylated(p)-Gsk3β,and β-catenin protein expressions following transfection with the Rab10-overexpressing AAV vector and a miRNA-103-3p inhibitor,alone or in combination,were analyzed using qRT-PCR and Western blotting.Results Injection of Rab10-overexpressing AVV vector into the lateral ventricle significantly improved depressive behaviors of CUMS rats.The mRNA and proteins expression of Rab10 were significantly down-regulated in the hippocampus of CUMS rats and in corticosterone-stimulated PC12 cells.Bioinformatics analysis and the results of double luciferase and RIP experiments confirmed the targeting relationship between miRNA-103-3p and Rab10.In PC12 cells,overexpression of Rab10 or silencing miRNA-103-3p activated the Wnt/β-catenin signaling pathway,up-regulated the expressions of BDNF,CREB and Beclin-1,and down-regulated the expression of p62 protein;silencing Rab10 obviously blocked the effect of miRNA-103-3p inhibitor.Conclusion In mouse models of depression,miRNA-103-3p activates Wnt/β-catenin signaling via targeting rab10 to improve neural plasticity and promotes neural cell autophagy.关键词
Rab10/miRNA-103-3p/神经可塑性/自噬/抑郁症Key words
Rab10/miRNA-103-3p/neural plasticity/autophagy/depression引用本文复制引用
张叶明,张袁祥,沈学彬,王国栋,朱磊..在抑郁症大鼠模型中MiRNA-103-3p调控Rab10促进神经细胞自噬[J].南方医科大学学报,2024,44(7):1315-1326,12.基金项目
安徽省高等学校自然科学重点研究项目(KJ2021A0858,2022AH051220) （KJ2021A0858,2022AH051220）
