Glutamate Corelease Promotes Growth and Survival of Midbrain Dopamine Neurons
Glutamate Corelease Promotes Growth and Survival of Midbrain Dopamine Neurons
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DOI：
10.1523/jneurosci.1939-12.2012
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发表时间：
2012-11-28
影响因子：
5.3
通讯作者：
Trudeau, Louis-Eric
中科院分区：
文献类型：
--
作者：
Fortin, Guillaume M.;Bourque, Marie-Josee;Trudeau, Louis-Eric
最近的研究表明，中纹状体多巴胺（DA）神经元的谷氨酸共释放调节了精神兴奋剂的行为激活。DA神经元释放谷氨酸的方式和时间可能发挥这一作用尚不清楚。考虑到在中脑DA神经元中2型泡状谷氨酸转运蛋白的早期表达，我们假设这种表型在发育过程中特别重要。使用条件基因敲除方法选择性地破坏小鼠DA神经元中的Vglut2基因，我们在体外和体内获得了中脑DA神经元生长和存活减少的证据，这与伏隔核DA神经支配密度降低、活动依赖性DA释放减少和运动行为受损有关。这些发现为谷氨酸能表型在中脑DA神经元发育中的功能作用提供了强有力的证据，为涉及中脑纹状体DA系统的神经退行性疾病的病理生理学开辟了新的视角。
Recent studies have proposed that glutamate corelease by mesostriatal dopamine (DA) neurons regulates behavioral activation by psychostimulants. How and when glutamate release by DA neurons might play this role remains unclear. Considering evidence for early expression of the type 2 vesicular glutamate transporter in mesencephalic DA neurons, we hypothesized that this cophenotype is particularly important during development. Using a conditional gene knock-out approach to selectively disrupt the Vglut2 gene in mouse DA neurons, we obtained in vitro and in vivo evidence for reduced growth and survival of mesencephalic DA neurons, associated with a decrease in the density of DA innervation in the nucleus accumbens, reduced activity-dependent DA release, and impaired motor behavior. These findings provide strong evidence for a functional role of the glutamatergic cophenotype in the development of mesencephalic DA neurons, opening new perspectives into the pathophysiology of neurodegenerative disorders involving the mesostriatal DA system.