囊泡GABA转运蛋白VGAT分布的本体变化与GABA作用的激发/抑制位移相关。,Neurochemistry international

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囊泡GABA转运蛋白VGAT分布的本体变化与GABA作用的激发/抑制位移相关。
Neurochemistry international ( IF 4.4 ) Pub Date : 2012-04-12 , DOI: 10.1016/j.neuint.2012.03.018
Jean-Luc Boulland ₁ , Farrukh A Chaudhry

Affiliation

GABA是成人中枢神经系统中主要的抑制性神经递质，并且与大神经元网络的同步有关。在发育过程中，GABA充当形态发生因子，并在许多大脑区域具有短暂的兴奋作用。已经鉴定出一种独特的蛋白质，水泡GABA转运蛋白（VGAT），在其胞吐释放之前将GABA累积到突触前小泡中。VGAT的功能及其分布在成人中已得到很好的定义，但是它对未成熟大脑中假定的GABA能神经末梢的短暂兴奋作用的贡献以及在假定的谷氨酸能神经末梢中的潜在作用仍然难以捉摸。我们已经研究了从胚胎后期到出生后几个阶段直至成年的VGAT在大脑中的表达。光学显微镜和电子显微镜下组织切片的定量免疫印迹和免疫标记显示，在出生后的前三周内，大脑皮层VGAT染色突然增加，类似于同时参与GABA合成和回收的其他蛋白质的增加框架-例如GAD65，GAD67，GAT1（Slc6a1）和SN1（Slc38a3）-与突触突增相吻合。VGAT表达的动态变化出现在许多细胞群体和不同大脑区域的几层中。但是，长满苔藓的光纤端子（MFT）避免了VGAT的染色。我们还证明了VGAT（+）神经末梢经历了发育重组，因此从主要针对未成熟大脑中几个大脑区域的主要神经元树突开始，它们针对成年人中相同细胞的体细胞。靶向亚细胞区室中的这种转变与跨神经元膜的氯化物梯度的转变相吻合，这表明对于GABA作用从激发到抑制的转变以及对神经元网络的有效同步的建立可能很重要。

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Ontogenetic changes in the distribution of the vesicular GABA transporter VGAT correlate with the excitation/inhibition shift of GABA action.

GABA is the major inhibitory neurotransmitter in the adult CNS and is among others involved in the synchronization of large neuronal networks. During development, GABA acts as a morphogenetic factor and has transient excitatory actions in many brain regions. One distinct protein, the vesicular GABA transporter (VGAT), has been identified accumulating GABA into presynaptic vesicles prior to its exocytotic release. The function of VGAT and its distribution is well defined in the adult, but its contribution to the transient excitatory action at putative GABAergic nerve terminals in the immature brain and its potential roles in putative glutamatergic nerve terminals remain elusive. We have studied VGAT expression in the brain from late embryonic stages through several postnatal stages until adulthood. Quantitative immunoblotting and immunolabeling of tissue sections at the light microscope and the electron microscope levels show an abrupt augmentation in VGAT staining in the cerebral cortex during the first three postnatal weeks, resembling the increase in other proteins involved in GABA synthesis and recycling in the same time frame - such as GAD65, GAD67, GAT1 (Slc6a1) and SN1 (Slc38a3) - and coincides with the synaptogenetic spurt. Dynamic changes in the expression of VGAT are seen in many cellular populations and in several layers in different brain regions. However, mossy fiber terminals (MFT) elude staining for VGAT. We also demonstrate that VGAT(+) nerve terminals undergo a developmental reorganization so that from targeting primarily the dendrites of the principal neurons in several brain regions in the immature brain, they target the soma of the same cells in the adult. This shift in the targeted subcellular compartment coincides with the conversion of the chloride gradient across neuronal membranes and suggests that it may be important for the shift of GABA action from excitation to inhibition and for the establishment of the potent synchronization of neuronal networks.

更新日期：2012-04-03

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