Cell Reports
Volume 16, Issue 6, 9 August 2016, Pages 1653-1663
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Article
miR-17-92 Cluster Regulates Adult Hippocampal Neurogenesis, Anxiety, and Depression

https://doi.org/10.1016/j.celrep.2016.06.101Get rights and content
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Highlights

  • miR-17-92 knockout and overexpression alter adult hippocampal neurogenesis

  • Expression levels of miR-17-92 affect mood and anxiety-like behaviors in mice

  • miR-17-92 regulates genes in the glucocorticoid pathway and targets Sgk1

  • miR-17-92 rescues reduced hippocampal proliferation caused by corticosterone

Summary

Emerging evidence has shown that noncoding RNAs, particularly microRNAs (miRNAs), contribute to the pathogenesis of mood and anxiety disorders, although the molecular mechanisms are poorly understood. Here, we show that altered levels of miR-17-92 in adult hippocampal neural progenitors have a significant impact on neurogenesis and anxiety- and depression-related behaviors in mice. miR-17-92 deletion in adult neural progenitors decreases neurogenesis in the dentate gyrus, while its overexpression increases neurogenesis. miR-17-92 affects neurogenesis by regulating genes in the glucocorticoid pathway, especially serum- and glucocorticoid-inducible protein kinase-1 (Sgk1). miR-17-92 knockout mice show anxiety- and depression-like behaviors, whereas miR-17-92 overexpressing mice exhibit anxiolytic and antidepression-like behaviors. Furthermore, we show that miR-17-92 expression in the adult mouse hippocampus responds to chronic stress, and miR-17-92 rescues proliferation defects induced by corticosterone in hippocampal neural progenitors. Our study uncovers a crucial role for miR-17-92 in adult neural progenitors through regulation of neurogenesis and anxiety- and depression-like behaviors.

Keywords

adult hippocampal neurogenesis
anxiety
depression
miR-17-92
Sgk1

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