Neuronal Nitric Oxide Synthase in Neural Stem Cells Induces Neuronal Fate Commitment via the Inhibition of Histone Deacetylase 2.
Active adult neurogenesis produces new functional neurons, which replace the lost ones and contribute to brain repair. Promoting neurogenesis may offer a therapeutic strategy for human diseases associated with neurodegeneration. Here, we report that endogenous neuronal nitric oxide synthase (nNOS) for neural stem cells (NSCs) or progenitors positively regulates neurogenesis. nNOS repression exhibits significantly decreased neuronal differentiation and nNOS upregulation promotes neurons production from NSCs. Using a quantitative approach, we show that instructive effect, that is instruction of NSCs to adopt a neuronal fate, contributes to the favorable effect of endogenous nNOS on neurogenesis. Furthermore, nNOS-mediated instruction of neuronal fate commitment is predominantly due to the reduction of histone deacetylase 2 (HDAC2) expression and enzymatic activity. Further investigation will be needed to test whether HDAC2 can serve as a new target for therapeutic intervention of neurodegenerative disorders.
Department of Pharmacy, the Affiliated Suzhou Municipal Hospital, Nanjing Medical University, Suzhou, China.
Xing
X
Jin
Department of Critical Care Medicine, the Affiliated Suzhou Municipal Hospital, Nanjing Medical University, Suzhou, China.
Zhang-Feng
ZF
Yu
Department of Pharmacy, the Affiliated Suzhou Municipal Hospital, Nanjing Medical University, Suzhou, China.
Fang
F
Chen
Department of Pharmacy, the Affiliated Suzhou Municipal Hospital, Nanjing Medical University, Suzhou, China.
Guang-Xian
GX
Lu
Department of Pharmacy, the Affiliated Suzhou Municipal Hospital, Nanjing Medical University, Suzhou, China.
Xin-Yuan
XY
Ding
Department of Pharmacy, the Affiliated Suzhou Municipal Hospital, Nanjing Medical University, Suzhou, China.
Lin-Jun
LJ
Xie
Department of Pharmacy, the Affiliated Suzhou Municipal Hospital, Nanjing Medical University, Suzhou, China.
Jian-Tong
JT
Sun
differentiation; histone deacetylase 2; neural stem cells; neurogenesis; neuronal nitric oxide synthase