SYNAPTIC VESICULAR MONAMINE TRANSPORTER

突触小泡单胺转运蛋白

• 批准号: 6431927
• 负责人: George Richard Uhl
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6431927
• 关键词: amphetamines; animal genetic material tag; complementary DNA; dopamine; dopamine transporter; embryonic stem cell; gene deletion mutation; genetic regulatory element; laboratory mouse; methylphenyltetrahydropyridine; molecular cloning; neurotoxicology; neurotoxins; neurotransmitter transport; nucleic acid sequence; synaptic vesicles; transcription factor; transfection /expression vector

Activities of the principal brain vesicular monamine transporter, VMAT2, are key to understanding the cellular compartmentalization of monoamines. They may play key roles in modulating the actions and neurotoxicities induced by amphetamine and by each of the toxins that selectively kills dopaminergic neurons to provide the best current models of Parkinson's disease. They could even play roles in normal age-related alterations in these systems. In this year, workers in this Branch continued to describ the poperties of knockout mice with deletions of the VMAT2 gene and other plasma membrane monaamine transporters. Aging studies documented clear reductions in locomotion, in amphetamine responsiveness and exaggerated age-related losses of dopaminergic markers in the heterozygous VMAT2 knockouts. Mice with deletions of VMAT2 and the plasma membrane transporters for DAT and SERT are viable and fertile and may display altered amphetamine responses. VMAT2 knockout mice continue to substantially enhance our understanding of mechanisms of age- related alterations in dopaminergic systema and actions of psychostimulants and locomotor systems.

主要脑囊泡单胺转运蛋白 VMAT2 的活性是了解单胺细胞区室化的关键。它们可能在调节安非他明和选择性杀死多巴胺能神经元的每种毒素诱导的作用和神经毒性方面发挥关键作用，以提供目前最好的帕金森病模型。它们甚至可以在这些系统中与年龄相关的正常变化中发挥作用。今年，该部门的工作人员继续描述了删除了VMAT2基因和其他质膜单胺转运蛋白的基因敲除小鼠的特性。衰老研究记录了杂合子 VMAT2 敲除中运动能力、安非他明反应性明显降低，以及与年龄相关的多巴胺能标记物的过度损失。缺失 VMAT2 以及 DAT 和 SERT 质膜转运蛋白的小鼠具有存活能力和生育能力，并且可能表现出改变的安非他明反应。 VMAT2 敲除小鼠继续大大增强我们对多巴胺能系统年龄相关改变机制以及精神兴奋剂和运动系统作用的理解。