title: miR-17-92 Cluster Regulates Adult Hippocampal Neurogenesis, Anxiety, and Depression.
abstract: 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.
authors.affiliation: Department of Cell and Developmental Biology, Cornell University Weill Medical College, 1300 York Avenue, Box 60, New York, NY 10065, USA.
authors.forename: Junghee
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Cell and Developmental Biology, Cornell University Weill Medical College, 1300 York Avenue, Box 60, New York, NY 10065, USA.
authors.forename: Seung-Nam
authors.initials: SN
authors.lastname: Kim
authors.affiliation: Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
authors.forename: Xuqing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cell and Developmental Biology, Cornell University Weill Medical College, 1300 York Avenue, Box 60, New York, NY 10065, USA.
authors.forename: Haijun
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Medicine and Institute for Computational Biomedicine, Cornell University Weill Medical College, New York, NY 10065, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Ji-Seon
authors.initials: JS
authors.lastname: Seo
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Cell and Developmental Biology, Cornell University Weill Medical College, 1300 York Avenue, Box 60, New York, NY 10065, USA. Electronic address: tas2009@med.cornell.edu.
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
mesh_terms: D000375:Aging; D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000473:pathology; D001522:Behavior, Animal / Q000502:physiology*; D003345:Corticosterone / Q000494:pharmacology; D003863:Depression / Q000235:genetics*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism
chemical_list: C575895:MIRN17-92 microRNA, mouse; D035683:MicroRNAs; D003345:Corticosterone
keywords: Sgk1; adult hippocampal neurogenesis; anxiety; depression; miR-17-92