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.

主要的脑囊泡单胺转运体VMAT2的活动是理解单胺的细胞区划的关键。它们可能在调节安非他明和每种毒素诱导的行为和神经毒性方面发挥关键作用，每种毒素选择性地杀死多巴胺能神经元，以提供目前最佳的帕金森氏病模型。他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。在这一年里，该分部的工作人员继续描述了VMAT2基因缺失和其他质膜单胺转运蛋白缺失的基因敲除小鼠的特征。衰老研究证明，在杂合子VMAT2基因敲除中，行走能力、苯丙胺反应性和与年龄相关的多巴胺能标志物的夸大丢失都明显减少。缺失VMAT2和DAT和SERT的质膜转运蛋白的小鼠是存活和可生育的，可能表现出苯丙胺反应的改变。VMAT2基因敲除小鼠继续显著提高我们对与年龄相关的多巴胺能系统改变的机制以及精神刺激剂和运动系统的作用的理解。