Moclobemide up-regulates proliferation of hippocampal progenitor cells in chronically stressed mice.
OBJECTIVE
To explore the action mechanism of antidepressants.


METHODS
The PC12 cell proliferation was detected by flow cytometry. The proliferation of hippocampal progenitor cells and level of brain-derived neurotrophic factor (BDNF) were measured by immunohistochemistry.


RESULTS
Treatment with N-methylaspartate (NMDA) 600 micromol/L for 3 d significantly decreased the percentage of S-phase in PC12 cells, while in the presence of classical antidepressant, moclobemide (MOC) 2 and 10 micromol/L, the percentage in S-phase increased. Furthermore, the proliferation of progenitor cells in hippocampal dentate gyrus (subgranular zone), as well as the level of BDNF in hippocampus significantly decreased in chronically stressed mice, while chronic administration with MOC 40 mg/kg (ip) up-regulated the progenitor cell proliferation and BDNF level in the same time course.


CONCLUSIONS
Up-regulation of the proliferation of hippocampal progenitor cells is one of the action mechanisms for MOC, which may be closely related to the elevation of BDNF level at the same time. These results also extend evidence for our hypothesis that up-regulation of the hippocampal neurogenesis is one of the common mechanisms for antidepressants.
Li
Yun-feng
YF
Beijing Institute of Pharmacology and Toxicology, China. lyf619@yahoo.com.cn
Zhang
You-zhi
YZ
Liu
Yan-qin
YQ
Wang
Heng-lin
HL
Yuan
Li
L
Luo
Zhi-pu
ZP
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology; D008297:Male; D051379:Mice; D020912:Moclobemide / Q000494:pharmacology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats; D016196:S Phase / Q000187:drug effects; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D013315:Stress, Psychological / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D008996:Monoamine Oxidase Inhibitors; D020912:Moclobemide