Progenitor proliferation in the adult hippocampus and substantia nigra induced by glial cell line-derived neurotrophic factor
Progenitor proliferation in the adult hippocampus and substantia nigra induced by glial cell line-derived neurotrophic factor
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DOI：
10.1016/j.expneurol.2005.07.010
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发表时间：
2005-11-01
影响因子：
5.3
通讯作者：
Gash, DM
中科院分区：
文献类型：
--
作者：
Chen, Y;Ai, Y;Gash, DM
神经发生在成年哺乳动物的海马和嗅球中是一个持续的过程，部分受营养因子调节。虽然神经胶质细胞系衍生神经营养因子（GDNF）在临床试验中被直接输送到大脑黑质纹状体系统治疗帕金森病，但其对大脑细胞发生的影响尚不清楚。在这里，我们研究了GDNF对海马和黑质两个GDNF反应区祖细胞增殖和分化的影响。2月龄大鼠纹状体注射GDNF (18 μ g/d) 28 d。采用5-溴-2-脱氧尿苷（BrdU）核结合鉴定新细胞，并采用光镜、电镜免疫染色和定量形态学技术进行分析。GDNF使海马和黑质细胞增殖分别增加78%和52%。在黑质中没有神经发生的证据，新细胞显示神经胶质特征，1549个brdu阳性细胞中没有一个共同标记多巴胺神经元标记物酪氨酸羟化酶（TH）。相反，GDNF上调了现有神经元中的TH，这与该热带因子的恢复作用一致。海马是一个支持成人神经发生的部位，这里产生的新细胞与齿状回的颗粒细胞密切相关。有些被双重标记为神经元标记物NeuN；另一些则具有星形胶质细胞的特征，星形胶质细胞是海马中新的成年神经元的主要来源。GDNF对海马的影响在记忆和学习过程中具有潜在的重要意义。(c) 2005爱思唯尔公司版权所有。
Neurogenesis is an ongoing process in the hippocampus and olfactory bulb of adult mammals, regulated in part by trophic factors. While glial cell line-derived neurotrophic factor (GDNF) is being directly delivered into the nigrostriatal system of the brain for the treatment of Parkinson's disease in clinical trials, little is known about its effects on cell genesis in the brain. Here, we investigated the effects of GDNF on progenitor cell proliferation and differentiation in two GDNF-responsive areas, the hippocampus and substantia nigra. GDNF (18 mu g/day) was infused in the striatum of 2-month-old Sprague-Dawley rats for 28 days. New cells were identified by the nuclear incorporation of 5-bromo-2-deoxyuridine (BrdU) and analyzed by light and electron microscopic immunostaining and quantitative morphometric techniques. GDNF significantly increased cell proliferation in the hippocampus by 78% and in the substantia nigra by 52%. There was no evidence of neurogenesis in the substantia nigra, with new cells displaying glial features and none of the 1549 BrdU-positive cells co-labeled for the dopamine neuronal marker tyrosine hydroxylase (TH). Rather, GDNF upregulated TH in existing neurons, consistent with the restorative actions of this tropic factor. The hippocampus is a site that supports adult neurogenesis and new cells generated here were closely associated with granule cells in the dentate gyrus. Some were double labeled for the neuronal marker NeuN; others had features of astrocytes, the principal source of new adult neurons in the hippocampus. The effects of GDNF on the hippocampus are potentially important in memory and learning processes. (c) 2005 Elsevier Inc. All rights reserved.