The Role of MiR-132 in Regulating Neural Stem Cell Proliferation, Differentiation and Neuronal Maturation

Cellular Physiology and Biochemistry

Dong Chen¹ 

关键词: Mir-132;    Neural stem cells;    Cell proliferation;    Differentiation;    Neuronal maturation;    Notch pathway;    ERK pathway;   

DOI  :  10.1159/000491543

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims microRNAs are of vital importance in neural development. As a brain-specific miRNA, miR-132 has been well studied in mature neurons. However, its role in neural stem cells (NSCs) remains unclear. In this study, we investigated the role of miR-132 in regulating NSCs proliferation, differentiation and neuronal maturation. Methods NSCs were obtained from fetal mice spinal cord. Proliferation, cell cycle, cell apoptosis, cell motility were measured through CCK-8, BrdU, AnnexinV-FITC/PI and migration assay respectively. The expression of synaptic proteins and ERK1/2 pathway were detected by western blot. The inactivation of Notch pathway was checked using qPCR. The neurite outgrowth was recorded using Image J software and Neuron J software. Dendritic length was further analyzed through sholl analysis. Fate determination of NSCs, developmental synapse formation was assessed by immunostaining. Results miR-132 negatively regulated NSCs proliferation by affecting the cell cycle and promoting apoptosis. Inactivated Notch-Hes1pathway was observed in miR-132 overexpression cells. miR-132 was significantly increased in differentiating NSCs following activation of ERK1/2 pathway. miR-132 could impair neuronal differentiation but promote glial cell differentiation by regulating Mecp2 expression. miR-132 was implicated in neurite outgrowth but slightly inhibited postsynaptic PSD-95 expression. The differentiated neurons exhibited normal electrophysiological characteristics, and already interacted with other neurons to form synaptic-like structures. Conclusion miR-132 was demonstrated as a negative regulator for NSCs self-renewal, neuronal differentiation but promoted glial cell differentiation and neurite outgrowth.

【 授权许可】

CC BY-NC-ND