Potential molecular mechanisms for decreased synaptic glutamate release in dysbindin-1 mutant mice.
Potential molecular mechanisms for decreased synaptic glutamate release in dysbindin-1 mutant mice.
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DOI：
10.1016/j.schres.2013.01.037
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发表时间：
2013-05
影响因子：
4.5
通讯作者：
Lavin A
中科院分区：
文献类型：
--
作者：
Saggu S;Cannon TD;Jentsch JD;Lavin A
人类的行为遗传学研究表明，DTNBP1基因的变异与精神分裂症及其认知缺陷表型有关。由DTNBP1编码的蛋白质-1在前脑神经元中表达，在那里它与介导囊泡运输和胞吐的蛋白质相互作用。已有研究表明，失结合蛋白-1会导致前额叶皮质谷氨酸释放减少；然而，这种减少的机制尚不完全清楚。为了研究这个问题，我们使用了前额叶皮质神经元的电生理记录、小泡的成像研究、钙动力学以及突触蛋白和钙离子通道的蛋白质印迹测量来评估dybindin-1缺失突变小鼠。与野生型对照相比，dybindin-1基因缺失的小鼠表现出可随时释放的突触小泡池的减少，量子大小的减少，释放的概率降低，内吞和胞吐的速率不足。此外，delbindin-1基因缺失的小鼠[Ca~(2+)]i、L和N型Ca~(2+)通道以及与突触小泡转运和启动有关的几种蛋白的表达降低。我们的研究结果为深入研究dybindin-1的作用机制提供了新的思路。
Behavioral genetic studies of humans have associated variation in the DTNBP1 gene with schizophrenia and its cognitive deficit phenotypes. The protein encoded by DTNBP1, dysbindin-1, is expressed in forebrain neurons where it interacts with proteins mediating vesicular trafficking and exocytosis. It has been shown that loss of dysbindin-1 results in a decrease in glutamate release in the prefrontal cortex; however the mechanisms underlying this decrease are not fully understood. In order to investigate this question, we evaluated dysbindin-1 null mutant mice, using electrophysiological recordings of prefrontal cortical neurons, imaging studies of vesicles, calcium dynamics and Western blot measures of synaptic proteins and Ca2+ channels. Dysbindin-1 null mice showed a decrease in the ready releasable pool of synaptic vesicles, decreases in quantal size, decreases in the probability of release and deficits in the rate of endo- and exocytosis compared with wild-type controls. Moreover, the dysbindin-1 null mice show decreases in the [Ca2+]i, expression of L- and N- type Ca2+ channels and several proteins involved in synaptic vesicle trafficking and priming. Our results provide new insights into the mechanisms of action of dysbindin-1.
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DOI：
10.1038/npp.2009.90
发表时间：
2009-11
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
16.2
作者：
BETZ, WJ;BEWICK, GS;RIDGE, RMAP
通讯作者：
RIDGE, RMAP
影响因子：
3.4
作者：
Khanna, Rajesh;Li, Qi;Stanley, Elise F.
通讯作者：
Stanley, Elise F.
影响因子：
1.8
作者：
Maher, Brion S.;Reimers, Mark A.;Kendler, Kenneth S.
通讯作者：
Kendler, Kenneth S.
DOI：
10.1126/science.1179685
发表时间：
2009-11-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Dickman DK;Davis GW
通讯作者：
Davis GW