title: Increased cellular turnover in response to fluoxetine in neuronal precursors derived from human embryonic stem cells.
abstract: Previous reports have shown that antidepressants increase neuronal cell proliferation and enhance neuroplasticity both in vivo and in vitro. This study investigated the direct effects of one such antidepressant, fluoxetine , on cell proliferation and on the production of neurotrophic factors in neuronal precursors derived from human embryonic stem cells (hESCs; H9). Fluoxetine induced the differentiation of neuronal precursors, strongly enhancing neuronal characteristics. The rate of proliferation was higher in fluoxetine -treated cells than in control cells, as determined by MTT [3(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide] assay. The CPDL (cumulative population doubling level) of the fluoxetine-treated cells was significantly increased in comparison to that of control cells (p<.001). Bromodeoxyuridine incorporation and staurosporine-induced apoptosis assays were elevated in fluoxetine-treated cells. Quantitative RT-PCR analysis revealed no significant differences in the expression of neurotrophic factors, brain-derived neurotrophic factor (BDNF);glial-derived neurotrophic factor (GDNF) and cAMP-responsive element-binding protein (CREB) between cells treated with fluoxetine for two weeks and their untreated counterparts. These results may help elucidate the mechanism of action of fluoxetine as a therapeutic drug for the treatment of depression. Data presented herein provide more evidence that, in addition to having a direct chemical effect on serotonin levels, fluoxetine can influence hESC-derived neuronal cells by increasing cell proliferation, while allowing them to maintain their neuronal characteristics.
authors: Animal Science, Michigan State University, East Lansing, MI 48824, USA.
authors: Eun-Ah
authors: EA
authors: Chang
authors: Zeki
authors: Z
authors: Beyhan
authors: Myung-Sik
authors: MS
authors: Yoo
authors: Kannika
authors: K
authors: Siripattarapravat
authors: Tak
authors: T
authors: Ko
authors: Keith J
authors: KJ
authors: Lookingland
authors: Burra V
authors: BV
authors: Madhukar
authors: Jose B
authors: JB
authors: Cibelli
mesh_terms: D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003866:Depressive Disorder / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005473:Fluoxetine / Q000494:pharmacology*; D006801:Humans; D009414:Nerve Growth Factors / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018687:Antidepressive Agents, Second-Generation; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D009414:Nerve Growth Factors; D005473:Fluoxetine; D001973:Bromodeoxyuridine