Blockade of microglial Cav1.2 Ca2+ channel exacerbates the symptoms in a Parkinson’s disease model
Blockade of microglial Cav1.2 Ca2+ channel exacerbates the symptoms in a Parkinson’s disease model
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DOI：
10.1038/s41598-019-45681-3
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发表时间：
2019-06
影响因子：
4.6
通讯作者：
Xinshuang Wang;H. Saegusa;Soontaraporn Huntula;T. Tanabe
中科院分区：
文献类型：
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作者：
Xinshuang Wang;H. Saegusa;Soontaraporn Huntula;T. Tanabe
Cav1.2通道是L型电压依赖性Ca2+通道，可被钙拮抗剂特异性阻断。电压依赖性 Ca2+ 通道通常被认为仅在神经元和肌肉细胞等兴奋性细胞中发挥作用，但最近有报道称它们在小胶质细胞等非兴奋性细胞中也发挥作用，小胶质细胞是先天免疫系统的关键参与者，并已被证明与帕金森病的病理生理学有关。在这里，我们证明了 Cav1.2 通道在小胶质细胞中表达，并且钙拮抗剂在体外增强了小胶质细胞的神经炎症 M1 转变并抑制了神经保护性 M2 转变。此外，在小胶质细胞特异性 Cav1.2 敲低小鼠中观察到 MPTP（一种诱导帕金森病样症状的神经毒素）中毒的多巴胺能神经元的强烈变性和伴随的行为缺陷，这表明小胶质细胞 Cav1.2 阻断对帕金森病产生有害影响。因此，小胶质细胞 Cav1.2 通道可能在生理条件下具有神经保护作用，也可能有助于疾病的恢复。
Cav1.2 channels are an L-type voltage-dependent Ca2+channel, which is specifically blocked by calcium antagonists. Voltage-dependent Ca2+channels are generally considered to be functional only in excitable cells like neurons and muscle cells, but recently they have been reported to also be functional in non-excitable cells like microglia, which are key players in the innate immune system and have been shown to be involved in the pathophysiology of Parkinson’s disease. Here, we show that Cav1.2 channels are expressed in microglia, and that calcium antagonists enhanced theneuroinflammatoryM1 transition and inhibitedneuroprotectiveM2 transition of microgliain vitro. Moreover, intensive degeneration of dopaminergic neurons and accompanying behavioural deficits were observed in microglia-specific Cav1.2 knockdown mice intoxicated with MPTP, a neurotoxin that induces Parkinson’s disease-like symptoms, suggesting detrimental effects of microglial Cav1.2 blockade on Parkinson’s disease. Therefore, microglial Cav1.2 channel may have neuroprotective roles under physiological conditions and may also contribute to recovery from disease conditions.