Endogenous and exogenous ciliary neurotrophic factor enhances forebrain neurogenesis in adult mice
Endogenous and exogenous ciliary neurotrophic factor enhances forebrain neurogenesis in adult mice
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DOI：
10.1016/s0014-4886(03)00129-8
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发表时间：
2003-10-01
影响因子：
5.3
通讯作者：
Hagg, T
中科院分区：
文献类型：
--
作者：
Emsley, JG;Hagg, T
成年哺乳动物中枢神经系统中的神经发生发生在脑室下区（SVZ）和齿状回。睫状神经营养因子（CNTF）的受体CNTFR α在成人脑室下区表达。由于CNTF在体外对神经前体细胞的作用是多种多样的，包括增殖和分化为神经元或胶质细胞，我们研究了其在体内的作用。成年C57 BL/6小鼠前脑注射CNTF后，两个神经原性区域内的BrdU标记细胞数均增加。在齿状回中，CNTF似乎也能增强前体细胞向神经元的分化，即，使NeuN+/BrdU+细胞比例从14%增加到29%，但不影响向星形胶质细胞（GFAP+）或少突胶质细胞（CN+）的分化。在SVZ中，CNTF使GFAP+ /BrdU+细胞的比例从接近1%增加到接近2%。CNTF可增加新生神经元向颗粒细胞层迁移的距离。脑室注射抗CNTF中和抗体可减少SVZ中BrdU标记细胞的数量。这些结果表明，内源性CNTF通过增加神经干细胞和/或前体细胞的增殖来调节成体神经发生。另外，CNTF可以维持细胞在S期更长的时间，导致BrdU标记增加。在SVZ的神经发生区域，CNTFR α仅存在于GFAP阳性的过程轴承细胞，这表明CNTF通过邻近的星形胶质细胞间接影响神经发生。或者，这些细胞可能是神经前体谱系的一部分。CNTF在神经系统内的有限表达使其成为细胞替代策略的潜在选择性药物靶点。(C)2003 Elsevier Science（美国）。All rights reserved.
Neurogenesis in the adult mammalian CNS occurs in the subventricular zone (SVZ) and dentate gyrus. The receptor for ciliary neurotrophic factor (CNTF), CNTFRalpha, is expressed in the adult subventricular zone. Because the in vitro effects of CNTF on neural precursors have been varied, including proliferation and differentiation into neurons or glia, we investigated its role in vivo. Injection of CNTF in the adult C57BL/6 mice forebrain increased the number of cells labeled with ip BrdU in both neurogenic regions. In the dentate gyrus, CNTF also appeared to enhance differentiation of precursors into neurons, i.e., increased the proportion of NeuN+/BrdU+ cells from similar to14 to similar to29%, but did not affect differentiation into astrocytes (GFAP+) or oligodendrocytes (CNPase+). In the SVZ, CNTF increased the proportion of GFAP+ /BrdU+ cells from similar to1 to similar to2%. CNTF enhanced the distance of migration of new neurons into the granule cell layer. Intraventricular injection of neutralizing anti-CNTF antibodies reduced the number of BrdU-Iabeled cells in the SVZ. These results suggest that endogenous CNTF regulates adult neurogenesis by increasing proliferation of neural stem cells and/or precursors. Alternatively, CNTF could maintain cells longer in the S-phase, resulting in increased BrdU labeling. In the neurogenic region of the SVZ, CNTFRalpha was exclusively present in GFAP-positive process-bearing cells, suggesting that CNTF affects neurogenesis indirectly via neighboring astroglia. Alternatively, these cells may be part of the neural precursor lineage. The restricted expression of CNTF within the nervous system makes it a potential selective drug target for cell replacement strategies. (C) 2003 Elsevier Science (USA). All rights reserved.