title: Paroxetine up-regulates neurogenesis in hippocampus-derived neural stem cell from fetal rats.
abstract: Paroxetine is a widely used antidepressant in clinic. Besides its role in inhibition of serotonin reuptake, resent studies indicate that the increase of hippocampal neurogenesis is also involved in its pharmacology. However, only limited data are available in this regard and its effect on the hippocampus-derived neural stem cell (NSCs) has not been well elucidated. In present study, we utilized hippocampus-derived NSCs from fetal rats to investigate the direct effect of paroxetine on the neurogenesis of NSCs and explore the possible cellular and molecular mechanisms. The results showed that paroxetine not only promoted the proliferation of NSCs, but also promoted NSCs to differentiate into neurons other than glial cells. In addition, the elevated protein levels of phosphorylated ERK1/2, Bcl-2, and brain-derived neurotrophic factor were also observed after paroxetine was administered. Furthermore, the proliferative effect and promotion of NSCs differentiating predominantly into neurons of paroxetine was inhibited by U0126, an ERK1/2 phosphorylation inhibitor. In conclusion, these data indicate that paroxetine can promote neurogenesis of neural stem cells, and this effect might be mediated by ERK1/2 signal pathways.
authors.affiliation: Department of Psychosomatic Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Zheng-Wu
authors.initials: ZW
authors.lastname: Peng
authors.forename: Fen
authors.initials: F
authors.lastname: Xue
authors.forename: Hua-Ning
authors.initials: HN
authors.lastname: Wang
authors.forename: Rui-Guo
authors.initials: RG
authors.lastname: Zhang
authors.forename: Yun-Chun
authors.initials: YC
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Li-Yi
authors.initials: LY
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Fan
authors.forename: Qing-Rong
authors.initials: QR
authors.lastname: Tan
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology; D049109:Cell Proliferation; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005333:Fetus / Q000166:cytology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D020935:MAP Kinase Signaling System; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D055495:Neurogenesis / Q000187:drug effects*; D009570:Nitriles / Q000494:pharmacology; D017374:Paroxetine / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018874:Spheroids, Cellular / Q000187:drug effects / Q000502:physiology; D014404:Tubulin / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018687:Antidepressive Agents, Second-Generation; D019208:Brain-Derived Neurotrophic Factor; D002070:Butadienes; D005904:Glial Fibrillary Acidic Protein; D009570:Nitriles; D019253:Proto-Oncogene Proteins c-bcl-2; D014404:Tubulin; C113580:U 0126; D017374:Paroxetine; D048049:Extracellular Signal-Regulated MAP Kinases