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首页> 外文期刊>Neurobiology of disease >Lack of CCR5 modifies glial phenotypes and population of the nigral dopaminergic neurons, but not MPTP-induced dopaminergic neurodegeneration
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Lack of CCR5 modifies glial phenotypes and population of the nigral dopaminergic neurons, but not MPTP-induced dopaminergic neurodegeneration

机译：CCR5的缺乏会改变神经胶质表型和黑色素多巴胺能神经元的人口，但不能改变MPTP诱导的多巴胺能神经变性。

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Constitutive expression of C-C chemokine receptor (CCR) 5 has been detected in astrocytes, microglia and neurons, but its physiological roles in the central nervous system are obscure. The bidirectional interactions between neuron and glial cells through CCR5 and its ligands were thought to be crucial for maintaining normal neuronal activities. No study has described function of CCR5 in the dopaminergic neurodegeneration in Parkinson's disease. In order to examine effects of CCR5 on l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration, we employed CCR5 wild type (WT) and knockout (KO) mice. Immunostainings for tyrosine hydroxylase (TH) exhibited that CCR5 KO mice had lower number of TH-positive neurons even in the absence of MPTP. Difference in MPTP (15mg/kg x 4 times, 2 hr interval-mediated loss of TH-positive neurons was subtle between CCR5 WT and KO mice, but there was larger dopamine depletion, behavioral impairments and microglial activation in CCR5 deficient mice. Intriguingly, CCR5 KO brains contained higher immunoreactivity for monoamine oxidase (MAO) B which was mainly localized within astrocytes. In agreement with upregulation of MAO B, concentration of MPP+ was higher in the substantia nigra and striatum of CCR5 KO mice after MPTP injection. We found remarkable activation of p38 MAPK in CCR5 deficient mice, which positively regulates MAO B expression. These results indicate that CCR5 deficiency modifies the nigrostriatal dopaminergic neuronal system and bidirectional interaction between neurons and glial cells via CCR5 might be important for dopaminergic neuronal survival.
机译：在星形胶质细胞，小胶质细胞和神经元中已检测到C-C趋化因子受体（CCR）5的组成型表达，但其在中枢神经系统中的生理作用尚不清楚。通过CCR5及其配体，神经元和神经胶质细胞之间的双向相互作用被认为对于维持正常的神经元活动至关重要。没有研究描述CCR5在帕金森氏病的多巴胺能神经变性中的功能。为了检查CCR5对1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的多巴胺能神经变性的影响，我们采用了CCR5野生型（WT）和基因敲除（KO）小鼠。酪氨酸羟化酶（TH）的免疫染色显示，即使没有MPTP，CCR5 KO小鼠的TH阳性神经元数量也较少。 CTP5 WT和KO小鼠的MPTP差异（15mg / kg x 4倍，间隔2小时间隔介导的TH阳性神经元的损失）微乎其微，但在CCR5缺陷的小鼠中多巴胺耗竭，行为障碍和小胶质细胞活化更大。 CCR5 KO脑对主要位于星形胶质细胞内的单胺氧化酶（MAO）B具有更高的免疫反应性，与MAO B的上调一致，MPTP注射后CCR5 KO小鼠的黑质和纹状体中MPP +的浓度更高。结果表明，CCR5缺乏会改变黑质纹状体多巴胺能神经元系统，而经由CCR5的神经元与神经胶质细胞之间的双向相互作用可能对多巴胺能神经元的存活很重要。

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