首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >mRNA for the EAAC1 subtype of glutamate transporter is present in neuronal dendrites in vitro and dramatically increases in vivo after a seizure.
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mRNA for the EAAC1 subtype of glutamate transporter is present in neuronal dendrites in vitro and dramatically increases in vivo after a seizure.

机译:谷氨酸转运蛋白EAAC1亚型的mRNA在体外存在于神经元树突中,癫痫发作后在体内急剧增加。

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摘要

The neuronal Na(+)-dependent glutamate transporter, excitatory amino acid carrier 1 (EAAC1, also called EAAT3), has been implicated in the control of synaptic spillover of glutamate, synaptic plasticity, and the import of cysteine for neuronal synthesis of glutathione. EAAC1 protein is observed in both perisynaptic regions of the synapse and in neuronal cell bodies. Although amino acid residues in the carboxyl terminal tail have been implicated in the dendritic targeting of EAAC1 protein, it is not known if mRNA for EAAC1 may also be targeted to dendrites. Sorting of mRNA to specific cellular domains provides a mechanism by which signals can rapidly increase translation in a local environment; this form of regulated translation has been linked to diverse biological phenomena ranging from establishment of polarity during embryogenesis to synapse development and synaptic plasticity. In the present study, EAAC1 mRNA sequences were amplified from dendritic samples that were mechanically harvested from low-density hippocampal neuronal cultures. In parallel analyses, mRNA for histone deacetylase 2 (HDAC-2) and glial fibrillary acidic protein (GFAP) was not detected, suggesting that these samples are not contaminated with cell body or glial mRNAs. EAAC1 mRNA also co-localized with Map2a (a marker of dendrites) but not Tau1 (a marker of axons) in hippocampal neuronal cultures by in situ hybridization. In control rats, EAAC1 mRNA was observed in soma and proximal dendrites of hippocampal pyramidal neurons. Following pilocarpine- or kainate-induced seizures, EAAC1 mRNA was present in CA1 pyramidal cell dendrites up to 200mum from the soma. These studies provide the first evidence that EAAC1 mRNA localizes to dendrites and suggest that dendritic targeting of EAAC1 mRNA is increased by seizure activity and may be regulated by neuronal activity/depolarization.
机译:神经元Na(+)依赖的谷氨酸转运蛋白,兴奋性氨基酸载体1(EAAC1,也称为EAAT3),与谷氨酸的突触溢出控制,突触可塑性和半胱氨酸的导入有关,用于神经元合成谷胱甘肽。在突触的突触周围区域和神经元细胞体中均观察到EAAC1蛋白。尽管在羧基末端尾部的氨基酸残基已经牵涉到EAAC1蛋白的树突靶向中,但是还不知道EAAC1的mRNA是否也可以靶向树突。将mRNA排序到特定的细胞结构域提供了一种机制,通过该机制信号可以在局部环境中快速增加翻译。这种形式的调控翻译与多种生物学现象有关,从胚胎形成期间的极性建立到突触发展和突触可塑性。在本研究中,EAAC1 mRNA序列是从低密度海马神经元培养物机械收获的树突状样品中扩增得到的。在平行分析中,未检测到组蛋白脱乙酰基酶2(HDAC-2)和神经胶质原纤维酸性蛋白(GFAP)的mRNA,这表明这些样品未受到细胞体或神经胶质mRNA的污染。通过原位杂交,EAAC1 mRNA在海马神经元培养物中也与Map2a(树突的标志物)共定位,而不与Tau1(轴突的标志物)共定位。在对照大鼠中,在海马锥体神经元的体细胞和近端树突中观察到EAAC1 mRNA。毛果芸香碱或海藻酸盐诱导的癫痫发作后,EAAC1 mRNA存在于距躯体最多200毫米的CA1锥体细胞树突中。这些研究提供了EAAC1 mRNA定位于树突的第一个证据,并表明癫痫发作活性增加了EAAC1 mRNA的树突状靶向,并且可能受到神经元活性/去极化的调节。

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