SYNAPTIC VESICULAR MONAMINE TRANSPORTER

主要的脑泡单胺转运蛋白VMAT2的活动是理解单胺细胞区隔化的关键。它们可能在调节由安非他明和每一种选择性杀死多巴胺能神经元的毒素引起的作用和神经毒性方面发挥关键作用，从而提供目前最好的帕金森病模型。它们甚至可能在这些系统中与年龄相关的正常变化中发挥作用。在这一年中，该分支的工作人员继续描述了VMAT2基因和其他质膜单胺转运体缺失的敲除小鼠的特性。衰老研究表明，在杂合的VMAT2基因敲除中，运动能力、安非他命反应性明显下降，多巴胺能标记物的年龄相关损失夸大。缺失VMAT2和DAT和SERT的质膜转运蛋白的小鼠可以存活和生育，并可能表现出改变的安非他明反应。VMAT2基因敲除小鼠继续大大提高了我们对多巴胺能系统和精神兴奋剂和运动系统作用的年龄相关改变机制的理解。

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.