PMID- 17912627 OWN - NLM STAT- MEDLINE DCOM- 20080807 LR - 20211020 IS - 0272-4340 (Print) IS - 0272-4340 (Linking) VI - 28 IP - 4 DP - 2008 Jun TI - Melatonin regulates the viability and differentiation of rat midbrain neural stem cells. PG - 569-79 AB - (1) Neurogenesis driven by neural stem cells (NSCs) is regulated by physiological and pathological factors. Melatonin (MT) has profound neurotrophic and neuroprotective effects. Hence, we studied the role of MT in regulating the viability and differentiation of NSCs derived from rat ventral midbrain. (2) NSCs were isolated from the rat ventral midbrain. The viability of NSCs was determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-ulfophenyl)-2H-tetrazolium assay. The differentiation of NSCs was examined by analyzing the expression of the neural markers, MT receptors, brain derived neurotropic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) with semi-quantitative RT-PCR, immunofluorescence cytochemistry, and Western blot. (3) Our results showed that MT could promote the viability of NSCs. In addition, MT could significantly elevate the mRNA and protein levels of tyroxine hydroxylase (TH), a marker of dopaminergic neurons, and decrease the expression of the astrocytes maker glial fibrillary acidic protein (GFAP). MT also increased the production of BDNF and GDNF in the cultured NSCs. Meanwhile, we first found that two subtypes of MT receptors, MT1 and MT2, were expressed in the ventral midbrain NSCs. (4) These results demonstrated that MT could induce NSCs to differentiate into dopaminergic neurons and decrease astrocyte production. These findings also suggest that MT could offer a beneficial tool in guiding directional differentiation of NSCs. FAU - Kong, Xiangying AU - Kong X AD - Department of Pharmacology, School of Basic Medicine, Peking Union Medical College and Institute of Basic Medical Science, Chinese Academy of Medical Sciences, 5 Dong Dan San Tiao, Beijing 100005, China. FAU - Li, Xuekun AU - Li X FAU - Cai, Zhe AU - Cai Z FAU - Yang, Nan AU - Yang N FAU - Liu, Yanyong AU - Liu Y FAU - Shu, Jun AU - Shu J FAU - Pan, Lin AU - Pan L FAU - Zuo, Pingping AU - Zuo P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071003 PL - United States TA - Cell Mol Neurobiol JT - Cellular and molecular neurobiology JID - 8200709 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptor, Melatonin, MT1) RN - 0 (Receptor, Melatonin, MT2) RN - JL5DK93RCL (Melatonin) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Cell Differentiation/*drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Dopamine/metabolism MH - Embryo, Mammalian MH - Embryonic Stem Cells/*drug effects/metabolism/physiology MH - Female MH - Gene Expression Regulation/drug effects MH - Melatonin/*pharmacology MH - Mesencephalon/*drug effects/metabolism/physiology MH - Neurons/*drug effects/metabolism/physiology MH - Pregnancy MH - Rats MH - Receptor, Melatonin, MT1/genetics/metabolism MH - Receptor, Melatonin, MT2/genetics/metabolism EDAT- 2007/10/04 09:00 MHDA- 2008/08/08 09:00 CRDT- 2007/10/04 09:00 PHST- 2007/05/06 00:00 [received] PHST- 2007/08/30 00:00 [accepted] PHST- 2007/10/04 09:00 [pubmed] PHST- 2008/08/08 09:00 [medline] PHST- 2007/10/04 09:00 [entrez] AID - 10.1007/s10571-007-9212-7 [doi] PST - ppublish SO - Cell Mol Neurobiol. 2008 Jun;28(4):569-79. doi: 10.1007/s10571-007-9212-7. Epub 2007 Oct 3.