Paroxetine up-regulates neurogenesis in hippocampus-derived neural stem cell from fetal rats
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Paroxetine up-regulates neurogenesis in hippocampus-derived neural stem cell from fetal rats Zheng-wu Peng • Fen Xue • Hua-ning Wang • Rui-guo Zhang • Yun-chun Chen • Ying Wang Li-yi Zhang • Juan Fan • Qing-rong Tan
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Received: 8 August 2012 / Accepted: 23 November 2012 / Published online: 5 January 2013 Ó Springer Science+Business Media New York 2013
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 hippocampusderived 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.
Zheng-wu Peng and Fen Xue contributed equally to this work. Z. Peng F. Xue H. Wang R. Zhang Y. Chen Y. Wang Q. Tan (&) Department of Psychosomatic Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China e-mail: [email protected] L. Zhang 102 Hospital, Changzhou 213003, China J. Fan Institute of Neuroscience, Fourth Military Medical University, Xi’an 710032, China
Keywords Paroxetine Neural stem cells Neuronal proliferation Neuronal differentiation ERK1/2
Major depression is a chronic disabling disorder. Although it is a social mortgage for its prevalent and recurrent [1], the etiology and responses to treatment were still unresolved. Resent evidence indicates that depression is accompanied by loss of neurons in the hippocampus, prefrontal cortex, amygdale, and basal ganglia [2], suggesting that neurodegeneration is one of pathways that are involved in occurrence of depression [3, 4]. Neurogenesis is a process of generating functionally integrated neurons from progenitor cells [5]. The hippocampus is a brain region that plays a critical role in learning and memory, and more importantly, it is one of a few brain regions where production of newborn neurons occurs throughout the lifetime [6, 7]. In adult central nervous system, newly born neurons are formed in the hippocampal subgranular zone (SGZ) of the dentate gyrus, and these newborn neuronal cells in the SGZ will also migrate to the granular cell
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