BDNF promotes differentiation and maturation of adult-born neurons through GABAergic transmission.
BDNF promotes differentiation and maturation of adult-born neurons through GABAergic transmission.
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DOI：
10.1523/jneurosci.0709-12.2012
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发表时间：
2012-10-10
期刊：
影响因子：
--
通讯作者：
Xu B
中科院分区：
文献类型：
--
作者：
Waterhouse EG;An JJ;Orefice LL;Baydyuk M;Liao GY;Zheng K;Lu B;Xu B
脑源性神经营养因子(BDNF)参与了齿状回颗粒下带(SGZ)成体神经发生的调控，但其调控机制尚不清楚。在本研究中，我们发现BDNF mRNA定位于从野生型小鼠分离的齿状回颗粒细胞的远端树突，而不是从Bdnfklox/KLOX小鼠分离的BDNF mRNA长3‘非翻译区(UTR)被截断的小鼠。KCL诱导的膜去极化刺激培养的海马神经元释放由长3‘非编码区BDNFm RNA翻译而来的树突状BDNF，但不能从短3’非编码区BDNFm RNA翻译而来。Bdnfklox/KLOX小鼠表现出谷氨酸脱羧酶65(一种GABA合成酶)的表达减少，前体细胞增殖增加，以及SGZ新生神经元的分化和成熟受损。使用GABAA受体活性增强剂苯巴比妥可以挽救成人神经发生的这些缺陷。此外，我们在小鼠中观察到了类似的神经发生缺陷，其中BDNF的受体TrkB在表达小白蛋白的GABA能中间神经元中选择性地被取消。因此，我们的数据表明，颗粒细胞树突中局部合成的BDNF至少部分地促进了表达小白蛋白的GABA能中间神经元的GABA释放，从而促进了SGZ内前体细胞的分化和成熟。
Brain-derived neurotrophic factor (BDNF) has been implicated in regulating adult neurogenesis in the subgranular zone (SGZ) of the dentate gyrus; however, the mechanism underlying this regulation remains unclear. In this study, we found that Bdnf mRNA localized to distal dendrites of dentate gyrus granule cells isolated from wild-type mice, but not from Bdnfklox/klox mice where the long 3′ untranslated region (UTR) of Bdnf mRNA is truncated. KCl-induced membrane depolarization stimulated release of dendritic BDNF translated from long 3′ UTR Bdnf mRNA in cultured hippocampal neurons, but not from short 3′ UTR Bdnf mRNA. Bdnfklox/klox mice exhibited reduced expression of glutamic acid decarboxylase 65 (a GABA synthase), increased proliferation of progenitor cells, and impaired differentiation and maturation of newborn neurons in the SGZ. These deficits in adult neurogenesis were rescued with administration of phenobarbital, an enhancer of GABAA receptor activity. Furthermore, we observed similar neurogenesis deficits in mice where the receptor for BDNF, TrkB, was selectively abolished in parvalbumin-expressing GABAergic interneurons. Thus, our data suggest that locally synthesized BDNF in dendrites of granule cells promotes differentiation and maturation of progenitor cells in the SGZ by enhancing GABA release, at least in part, from parvalbumin-expressing GABAergic interneurons.