PMID- 12798291 OWN - NLM STAT- MEDLINE DCOM- 20030711 LR - 20220310 IS - 0012-1606 (Print) IS - 0012-1606 (Linking) VI - 258 IP - 2 DP - 2003 Jun 15 TI - Nitric oxide acts in a positive feedback loop with BDNF to regulate neural progenitor cell proliferation and differentiation in the mammalian brain. PG - 319-33 AB - Nitric oxide (NO) is believed to act as an intercellular signal that regulates synaptic plasticity in mature neurons. We now report that NO also regulates the proliferation and differentiation of mouse brain neural progenitor cells (NPCs). Treatment of dissociated mouse cortical neuroepithelial cluster cell cultures with the NO synthase inhibitor L-NAME or the NO scavenger hemoglobin increased cell proliferation and decreased differentiation of the NPCs into neurons, whereas the NO donor sodium nitroprusside inhibited NPC proliferation and increased neuronal differentiation. Brain-derived neurotrophic factor (BDNF) reduced NPC proliferation and increased the expression of neuronal NO synthase (nNOS) in differentiating neurons. The stimulatory effect of BDNF on neuronal differentation of NPC was blocked by L-NAME and hemoglobin, suggesting that NO produced by the latter cells inhibited proliferation and induced neuronal differentiation of neighboring NPCs. A similar role for NO in regulating the switch of neural stem cells from proliferation to differentiation in the adult brain is suggested by data showing that NO synthase inhibition enhances NPC proliferation and inhibits neuronal differentiation in the subventricular zone of adult mice. These findings identify NO as a paracrine messenger stimulated by neurotrophin signaling in newly generated neurons to control the proliferation and differentiation of NPC, a novel mechanism for the regulation of developmental and adult neurogenesis. FAU - Cheng, Aiwu AU - Cheng A AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. FAU - Wang, Shuqin AU - Wang S FAU - Cai, Jingli AU - Cai J FAU - Rao, Mahendra S AU - Rao MS FAU - Mattson, Mark P AU - Mattson MP LA - eng PT - Journal Article PL - United States TA - Dev Biol JT - Developmental biology JID - 0372762 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Enzyme Inhibitors) RN - 0 (RNA, Messenger) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type I) RN - EC 1.14.13.39 (Nos1 protein, mouse) RN - EC 2.7.10.1 (Receptor, trkB) RN - V55S2QJN2X (NG-Nitroarginine Methyl Ester) SB - IM MH - Animals MH - Base Sequence MH - Brain/*cytology/*embryology/growth & development/metabolism MH - Brain-Derived Neurotrophic Factor/pharmacology/*physiology MH - Cell Differentiation/physiology MH - Cell Division/physiology MH - Cells, Cultured MH - Enzyme Inhibitors/pharmacology MH - Feedback MH - Female MH - Mice MH - Mice, Inbred C57BL MH - NG-Nitroarginine Methyl Ester/pharmacology MH - Neurons/cytology/metabolism MH - Nitric Oxide/*physiology MH - Nitric Oxide Synthase/antagonists & inhibitors/biosynthesis MH - Nitric Oxide Synthase Type I MH - Pregnancy MH - RNA, Messenger/genetics/metabolism MH - Receptor, trkB/genetics/metabolism MH - Signal Transduction MH - Stem Cells/cytology/metabolism EDAT- 2003/06/12 05:00 MHDA- 2003/07/12 05:00 CRDT- 2003/06/12 05:00 PHST- 2003/06/12 05:00 [pubmed] PHST- 2003/07/12 05:00 [medline] PHST- 2003/06/12 05:00 [entrez] AID - S0012160603001209 [pii] AID - 10.1016/s0012-1606(03)00120-9 [doi] PST - ppublish SO - Dev Biol. 2003 Jun 15;258(2):319-33. doi: 10.1016/s0012-1606(03)00120-9.