Dynamic changes in vesicular glutamate transporter 1 function and expression related to methamphetamine-induced glutamate release.

Mark KA; Quinton MS; Russek SJYamamoto BK

首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Dynamic changes in vesicular glutamate transporter 1 function and expression related to methamphetamine-induced glutamate release.

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Dynamic changes in vesicular glutamate transporter 1 function and expression related to methamphetamine-induced glutamate release.

机译：囊泡谷氨酸转运蛋白 1 功能和表达的动态变化与甲基苯丙胺诱导的谷氨酸释放有关。

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The vesicular glutamate (GLU) transporter (VGLUT1) is a critical component of glutamatergic neurons that regulates GLU release. Despite the likely role of GLU release in drug abuse pathology, there is no information that links VGLUT1 with drugs of abuse. This study provides the first evidence that methamphetamine (METH) alters the dynamic regulation of striatal VGLUT1 function and expression through a polysynaptic pathway. METH increases cortical VGLUT1 mRNA, striatal VGLUT1 protein in subcellular fractions, and the Vmax of striatal vesicular GLU uptake. METH also increases glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein in the crude vesicle fraction. METH-induced increases in cortical VGLUT1 mRNA, as well as striatal VGLUT1 and GAPDH, are GABA(A) receptor-dependent because they are blocked by GABA(A) receptor antagonism in the substantia nigra. These results show that VGLUT1 can be dynamically regulated via a polysynaptic pathway to facilitate vesicular accumulation of GLU for subsequent release after METH.

机译：囊泡谷氨酸（GLU）转运蛋白（VGLUT1）是调节 GLU 释放的谷氨酸能神经元的关键成分。尽管 GLU 释放可能在药物滥用病理学中发挥作用，但没有信息将 VGLUT1 与滥用药物联系起来。本研究首次证明甲基苯丙胺（METH）通过多突触途径改变纹状体 VGLUT1 功能和表达的动态调节。METH 增加皮质 VGLUT1 mRNA、亚细胞组分中的纹状体 VGLUT1 蛋白和纹状体囊泡 GLU 摄取的 Vmax。METH 还增加粗囊泡组分中的甘油醛-3-磷酸脱氢酶（GAPDH）蛋白。METH 诱导的皮质 VGLUT1 mRNA 以及纹状体 VGLUT1 和 GAPDH 的增加是 GABA（A）受体依赖性的，因为它们被黑质中的 GABA（A）受体拮抗作用阻断。这些结果表明，VGLUT1 可以通过多突触途径动态调节，以促进 GLU 的囊泡积累，以便在 METH 后随后释放。

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《The Journal of Neuroscience: The Official Journal of the Society for Neuroscience》 |2007年第25期|6823-6831|共9页
作者
Mark KA; Quinton MS; Russek SJYamamoto BK;
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作者单位

Laboratory of Neurochemistry, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts 02118, USA. Neuroscience;

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正文语种英语
中图分类神经病学与精神病学;
关键词
Gene Expression Regulation; Glutamic Acid; Methamphetamine; Vesicular Glutamate Transport Protein 1; 基因表达调控; 谷氨酸; 甲基苯丙胺;

机译：基因表达调控;谷氨酸;甲基苯丙胺;囊泡谷氨酸转运蛋白1;基因表达调控;谷氨酸;甲基苯丙胺;

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Dynamic changes in vesicular glutamate transporter 1 function and expression related to methamphetamine-induced glutamate release.

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