title: Secreted frizzled-related protein 3 regulates activity-dependent adult hippocampal neurogenesis.
abstract: Adult neurogenesis, the process of generating mature neurons from adult neural stem cells, proceeds concurrently with ongoing neuronal circuit activity and is modulated by various physiological and pathological stimuli. The niche mechanism underlying the activity-dependent regulation of the sequential steps of adult neurogenesis remains largely unknown. Here, we report that neuronal activity decreases the expression of secreted frizzled-related protein 3 (sFRP3), a naturally secreted Wnt inhibitor highly expressed by adult dentate gyrus granule neurons. Sfrp3 deletion activates quiescent radial neural stem cells and promotes newborn neuron maturation, dendritic growth, and dendritic spine formation in the adult mouse hippocampus. Furthermore, sfrp3 reduction is essential for activity-induced adult neural progenitor proliferation and the acceleration of new neuron development. Our study identifies sFRP3 as an inhibitory niche factor from local mature dentate granule neurons that regulates multiple phases of adult hippocampal neurogenesis and suggests an interesting activity-dependent mechanism governing adult neurogenesis via the acute release of tonic inhibition.
authors: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. jang.mihyeon@mayo.edu
authors: Mi-Hyeon
authors: MH
authors: Jang
authors: Michael A
authors: MA
authors: Bonaguidi
authors: Yasuji
authors: Y
authors: Kitabatake
authors: Jiaqi
authors: J
authors: Sun
authors: Juan
authors: J
authors: Song
authors: Eunchai
authors: E
authors: Kang
authors: Heechul
authors: H
authors: Jun
authors: Chun
authors: C
authors: Zhong
authors: Yijing
authors: Y
authors: Su
authors: Junjie U
authors: JU
authors: Guo
authors: Marie Xun
authors: MX
authors: Wang
authors: Kurt A
authors: KA
authors: Sailor
authors: Ju-Young
authors: JY
authors: Kim
authors: Yuan
authors: Y
authors: Gao
authors: Kimberly M
authors: KM
authors: Christian
authors: Guo-li
authors: GL
authors: Ming
authors: Hongjun
authors: H
authors: Song
mesh_terms: D000818:Animals; D005260:Female; D006624:Hippocampus / Q000166:cytology*; D017403:In Situ Hybridization; D051379:Mice; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D010862:Pilocarpine / Q000494:pharmacology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D010862:Pilocarpine; D011506:Proteins; D000094742:Secreted Frizzled-Related Proteins
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