Localization and expression of group I metabotropic glutamate receptors in the mouse striatum, globus pallidus, and subthalamic nucleus: Regulatory effects of MPTP treatment and constitutive Homer deletion
Localization and expression of group I metabotropic glutamate receptors in the mouse striatum, globus pallidus, and subthalamic nucleus: Regulatory effects of MPTP treatment and constitutive Homer deletion
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DOI：
10.1523/jneurosci.3819-06.2007
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发表时间：
2007-06-06
影响因子：
5.3
通讯作者：
Smith, Yoland
中科院分区：
文献类型：
--
作者：
Kuwajima, Masaaki;Dehoff, Marlin H.;Smith, Yoland
第一组代谢型谷氨酸受体（mGluRs），mGluR 1和mGluR 5，调节苍白球（GP）和丘脑底核（BTH）的活动。为了测试I组mGluRs的定位是否在帕金森综合征中改变，我们使用免疫电子显微镜来分析mGluR 1a和mGluR 5在1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）处理的小鼠的GP和纹状体中的亚细胞和突触下分布。Homer 1和Homer 2基因敲除小鼠用于评估Homer在MPTP诱导的I组mGluRs再分布中的作用。我们还研究了MPTP对GP和纹状体中I组mGluRs和Homer蛋白表达水平的影响。MPTP处理显著降低纹状体中H1 a和mGluR 1a的表达水平，但不影响GP。虽然光学显微镜没有发现明显的影响，MPTP治疗组I mGluRs和荷马蛋白的分布在GP和GP，在超微结构定位的mGluR 1a的具体变化，发现在MPTP治疗的正常和荷马基因敲除小鼠。突触前轴突和末端mGluR 1a标记的表达增加，并且在假定的GABA能突触的突触后特化中mGluR 1a免疫反应性水平增加，是多巴胺耗竭诱导的最显著的效应之一。然而，这些变化都没有发现mGluR 5，相比之下，显示复杂的调节变化，其突触下分布在响应荷马缺失和MPTP病变。因此，黑质纹状体多巴胺能损伤和Homer缺失导致体内I组mGluRs的运输变化，其对受体亚型和脑区具有特异性。
Group I metabotropic glutamate receptors (mGluRs), mGluR1 and mGluR5, regulate activity in the globus pallidus (GP) and subthalamic nucleus (STN). To test whether the localization of group I mGluRs is altered in parkinsonism, we used immunoelectron microscopy to analyze the subcellular and subsynaptic distribution of mGluR1a and mGluR5 in GP and STN of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Homer1 and Homer2 knock-out mice were used to assess the role of Homer in MPTP-induced redistribution of group I mGluRs. We also examined the effects of MPTP on the expression levels of group I mGluRs and Homer proteins in GP and striatum. MPTP treatment significantly reduced the expression levels of H1a and mGluR1a in striatum but not in GP. Although light microscopy did not reveal noticeable effects of MPTP treatment on the distribution of group I mGluRs and Homer proteins in GP and STN, specific changes in the ultrastructural localization of mGluR1a were found in MPTP-treated normal and Homer knock-out mice. An increase in the expression of presynaptic axonal and terminal mGluR1a labeling and an increased level of mGluR1a immunoreactivity in the postsynaptic specialization of putative GABAergic synapses were among the most significant effects induced by dopamine depletion. However, neither of these changes was found for mGluR5, which, in contrast, displayed complex regulatory alterations in its subsynaptic distribution in response to Homer deletion and MPTP lesion. Thus, nigrostriatal dopaminergic lesion and Homer deletion lead to changes in the trafficking of group I mGluRs in vivo that are specific to receptor subtypes and brain areas.