Adenovirally expressed noggin and brain-derived neurotrophic factor cooperate to induce new medium spiny neurons from resident progenitor cells in the adult striatal ventricular zone
Adenovirally expressed noggin and brain-derived neurotrophic factor cooperate to induce new medium spiny neurons from resident progenitor cells in the adult striatal ventricular zone
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DOI：
10.1523/jneurosci.1554-03.2004
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发表时间：
2004-03-03
影响因子：
5.3
通讯作者：
Goldman, SA
中科院分区：
文献类型：
--
作者：
Chmielnicki, E;Benraiss, A;Goldman, SA
成体前脑室壁内源性祖细胞的神经发生可能是由同源神经元分化剂（特别是 BDNF）的局部病毒过度表达诱导的。在这里，我们发现 noggin 的过度表达，通过抑制室管膜下祖细胞的神经胶质分化，可以增强腺病毒 BDNF 介导的新神经元向成年大鼠新纹状体的募集。新神经元在室管膜下区形成后至少存活 2 个月，并主要作为尾壳核中的 GABA 能 DARPP-32(+) 中型多刺神经元被招募。新的中等多刺神经元成功投射到苍白球（它们通常的发育目标），将过程延伸到正常成人纹状体的几毫米。因此，同时抑制室管膜下神经胶质分化和促进神经元分化可以动员内源性室管膜下祖细胞，以实现对成人大脑的其他非神经源性区域的大量神经元添加。
Neurogenesis from endogenous progenitor cells in the adult forebrain ventricular wall may be induced by the local viral overexpression of cognate neuronal differentiation agents, in particular BDNF. Here, we show that the overexpression of noggin, by acting to inhibit glial differentiation by subependymal progenitor cells, can potentiate adenoviral BDNF-mediated recruitment of new neurons to the adult rat neostriatum. The new neurons survive at least 2 months after their genesis in the subependymal zone and are recruited primarily as GABAergic DARPP-32(+) medium spiny neurons in the caudate-putamen. The new medium spiny neurons successfully project to the globus pallidus, their usual developmental target, extending processes over several millimeters of the normal adult striatum. Thus, concurrent suppression of subependymal glial differentiation and promotion of neuronal differentiation can mobilize endogenous subependymal progenitor cells to achieve substantial neuronal addition to otherwise non-neurogenic regions of the adult brain.