GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3
GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3
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DOI：
10.1016/j.bbrc.2013.04.011
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发表时间：
2013-05-17
影响因子：
3.1
通讯作者：
Kusumi, Ichiro
中科院分区：
文献类型：
--
作者：
Boku, Shuken;Nakagawa, Shin;Kusumi, Ichiro
虽然抗抑郁药在成年海马齿状回(DG)的促神经源性作用被认为是抗抑郁药物发挥治疗作用的机制之一，但抗抑郁药并不促进成年DG来源的神经前体细胞的增殖。鉴于已有研究表明，抗抑郁药可促进大鼠星形胶质细胞来源的C6胶质瘤细胞表达和分泌胶质细胞源性神经营养因子(GDNF)，GDNF可促进成年DG的神经发生，因此，我们研究了GDNF对成年DG来源的神经前体细胞增殖、分化和凋亡的影响。数据显示，GDNF促进神经前体细胞向星形胶质细胞分化，但对其增殖和凋亡无影响。此外，GDNF增加了STAT3的磷酸化，STAT3的特异性抑制剂和针对STAT3的慢病毒shRNA都减少了它们向星形胶质细胞的分化。综上所述，我们的研究结果表明，GDNF通过激活STAT3促进成年DG神经前体细胞星形胶质细胞的形成，这一作用可能间接影响神经发生。(C)2013 Elsevier Inc.保留所有权利。
While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression and secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis. (C) 2013 Elsevier Inc. All rights reserved.