B6eGFPChAT mice overexpressing the vesicular acetylcholine transporter exhibit spontaneous hypoactivity and enhanced exploration in novel environments.
B6eGFPChAT mice overexpressing the vesicular acetylcholine transporter exhibit spontaneous hypoactivity and enhanced exploration in novel environments.
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DOI：
10.1002/brb3.139
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发表时间：
2013-07
影响因子：
3.1
通讯作者：
Aubert I
中科院分区：
文献类型：
--
作者：
Nagy PM;Aubert I
胆碱能神经支配广泛地遍及中枢和周围神经系统。在其众多作用中，神经递质乙酰胆碱（ACh）有助于调节运动功能、运动和探索。神经退行性疾病，特别是阿尔茨海默病（AD）的胆碱能缺陷和替代策略已被研究。目前研究的重点是阻断乙酰胆碱酯酶（AChE）和增强乙酰胆碱酯酶的合成以改善胆碱能神经传递。作为通过上调囊泡乙酰胆碱转运体（VAChT）来评估胆碱能功能增强的生理效应的第一步，我们使用了高胆碱能B6eGFPChAT基因小鼠模型，该模型已被证明含有多个VAChT基因拷贝。生化和行为范式分析表明，适度增加VAChT表达对自发运动、对新刺激的反应和对新环境的适应有重要影响。这些观察结果支持VAChT作为增强胆碱能张力的治疗靶点的潜力，从而减少自发性多动和增加对新环境的探索。
Cholinergic innervation is extensive throughout the central and peripheral nervous systems. Among its many roles, the neurotransmitter acetylcholine (ACh) contributes to the regulation of motor function, locomotion, and exploration. Cholinergic deficits and replacement strategies have been investigated in neurodegenerative disorders, particularly in cases of Alzheimer's disease (AD). Focus has been on blocking acetylcholinesterase (AChE) and enhancing ACh synthesis to improve cholinergic neurotransmission. As a first step in evaluating the physiological effects of enhanced cholinergic function through the upregulation of the vesicular acetylcholine transporter (VAChT), we used the hypercholinergic B6eGFPChAT congenic mouse model that has been shown to contain multiple VAChT gene copies. Analysis of biochemical and behavioral paradigms suggest that modest increases in VAChT expression can have a significant effect on spontaneous locomotion, reaction to novel stimuli, and the adaptation to novel environments. These observations support the potential of VAChT as a therapeutic target to enhance cholinergic tone, thereby decreasing spontaneous hyperactivity and increasing exploration in novel environments.
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影响因子：
2.5
作者：
de Castro, B. M.;Pereira, G. S.;Prado, M. A. M.
通讯作者：
Prado, M. A. M.
影响因子：
9.8
作者：
Guzman, Monica S.;De Jaeger, Xavier;Prado, Marco A. M.
通讯作者：
Prado, Marco A. M.
影响因子：
5.3
作者：
de Castro, Braulio M.;De Jaeger, Xavier;Prado, Vania F.
通讯作者：
Prado, Vania F.
影响因子：
5
作者：
File, SE;Cheeta, S;Kenny, PJ
通讯作者：
Kenny, PJ
DOI：
10.1523/jneurosci.2056-10.2010
发表时间：
2010-07-21
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Drenan RM;Grady SR;Steele AD;McKinney S;Patzlaff NE;McIntosh JM;Marks MJ;Miwa JM;Lester HA
通讯作者：
Lester HA