Comprehensive behavioral study of mGluR3 knockout mice: implication in schizophrenia related endophenotypes.
Comprehensive behavioral study of mGluR3 knockout mice: implication in schizophrenia related endophenotypes.
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DOI：
10.1186/1756-6606-7-31
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发表时间：
2014-04-23
期刊：
影响因子：
3.6
通讯作者：
Fukumaki Y
中科院分区：
文献类型：
--
作者：
Fujioka R;Nii T;Iwaki A;Shibata A;Ito I;Kitaichi K;Nomura M;Hattori S;Takao K;Miyakawa T;Fukumaki Y
我们先前进行了谷氨酸受体基因家族成员与精神分裂症的系统关联研究，并发现GRM 3（代谢型谷氨酸受体3：mGluR 3的基因）的多态性与该疾病呈正相关。GRM 3在脑功能中的生理作用及其在精神分裂症发病机制中的功能作用仍有待解决。我们产生了mGluR 3敲除（KO）小鼠并进行了全面的行为分析。KO小鼠在旷场、亮/暗转换和24小时笼舍监测测试中表现出多动，在Porsolt强迫游泳测试中表现出对压力事件的参考记忆受损，在线索和背景恐惧条件反射测试中表现出背景记忆受损，在T迷宫强迫交替任务测试中表现出工作记忆受损。多动症和工作记忆受损被称为精神分裂症的内在表型。我们通过评估KO和野生型（WT）小鼠海马CA 1区的长时程增强（LTP）来研究长时程突触可塑性。我们观察到两种基因型之间的LTP的幅度没有差异，这表明mGluR 3是不是必不可少的LTP在小鼠海马CA 1区。由于多动症通常与多巴胺能传递增加有关，我们在体内进行了KO和WT小鼠中脑核细胞外多巴胺的微透析测量。我们观察到增强甲基苯丙胺（MAP）诱导的释放多巴胺基因敲除小鼠。这些结果表明，谷氨酸-多巴胺相互作用的干扰可能参与精神分裂症样行为的病理生理学，如mGluR 3 KO小鼠的活动过度。
We previously performed systematic association studies of glutamate receptor gene family members with schizophrenia, and found positive associations of polymorphisms in the GRM3 (a gene of metabotropic glutamate receptor 3: mGluR3) with the disorder. Physiological roles of GRM3 in brain functions and its functional roles in the pathogenesis of schizophrenia remain to be resolved. We generated mGluR3 knockout (KO) mice and conducted comprehensive behavioral analyses. KO mice showed hyperactivity in the open field, light/dark transition, and 24-hour home cage monitoring tests, impaired reference memory for stressful events in the Porsolt forced swim test, impaired contextual memory in cued and contextual fear conditioning test, and impaired working memory in the T-Maze forced alternation task test. Hyperactivity and impaired working memory are known as endophenotypes of schizophrenia. We examined long-term synaptic plasticity by assessing long-term potentiation (LTP) in the CA1 region in the hippocampi of KO and wild-type (WT) mice. We observed no differences in the amplitude of LTP between the two genotypes, suggesting that mGluR3 is not essential for LTP in the CA1 region of the mouse hippocampus. As hyperactivity is typically associated with increased dopaminergic transmission, we performed in vivo microdialysis measurements of extracellular dopamine in the nucleus accumbens of KO and WT mice. We observed enhancements in the methamphetamine (MAP)-induced release of dopamine in KO mice. These results demonstrate that a disturbance in the glutamate-dopamine interaction may be involved in the pathophysiology of schizophrenia-like behavior, such as hyperactivity in mGluR3 KO mice.
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影响因子：
4.6
作者：
Ikegami M;Uemura T;Kishioka A;Sakimura K;Mishina M
通讯作者：
Mishina M
影响因子：
3.8
作者：
Amann, Laura C.;Gandal, Michael J.;Siegel, Steven J.
通讯作者：
Siegel, Steven J.
影响因子：
5.6
作者：
Moessner, Rainald;Schuhmacher, Anna;Maier, Wolfgang
通讯作者：
Maier, Wolfgang
DOI：
10.3791/1088
发表时间：
2008-12-22
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Komada, Munekazu;Takao, Keizo;Miyakawa, Tsuyoshi
通讯作者：
Miyakawa, Tsuyoshi
影响因子：
4.7
作者：
Ito, I;Kawakami, R;Sugiyama, H
通讯作者：
Sugiyama, H