Knockdown of microglial Cav2.2 N‐type voltage‐dependent Ca 2+ channel ameliorates behavioral deficits in a mouse model of Parkinson’s disease,FEBS Letters

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Knockdown of microglial Cav2.2 N‐type voltage‐dependent Ca 2+ channel ameliorates behavioral deficits in a mouse model of Parkinson’s disease
FEBS Letters ( IF 3.0 ) Pub Date : 2020-06-16 , DOI: 10.1002/1873-3468.13853
Hironao Saegusa ₁ , Xu Li ₁ , Xinshuang Wang ₁ , Midori Kayakiri ₁ , Tsutomu Tanabe ₁

Affiliation

Cav2.2 N‐type voltage‐dependent Ca2+ channel (VDCC) expressed in neurons is known to be essential for neurotransmitter release. We have shown previously that this channel is also expressed in nonexcitable microglia and plays pivotal roles in microglial functions. Here, we have examined the effects of microglia‐specific knockdown (KD) of Cav2.2 channel in a mouse model of Parkinson’s disease (PD). We found that the KD of Cav2.2 channel reduces the accumulation of microglia in the substantia nigra and ameliorates the behavioral deficits in PD model mice. These results are in marked contrast with those found in microglia‐specific KD of Cav1.2 L‐type channel, where exacerbated symptoms are observed. Our results suggest that blockade of microglial Cav2.2 N‐type VDCC is beneficial for the treatment of PD.

中文翻译：

敲除小胶质细胞 Cav2.2 N 型电压依赖性 Ca 2+ 通道可改善帕金森病小鼠模型的行为缺陷

已知神经元中表达的 Cav2.2 N 型电压依赖性 Ca2+ 通道 (VDCC) 对神经递质释放至关重要。我们之前已经表明，该通道也在非兴奋性小胶质细胞中表达，并在小胶质细胞功能中发挥关键作用。在这里，我们检查了 Cav2.2 通道的小胶质细胞特异性敲低 (KD) 在帕金森病 (PD) 小鼠模型中的影响。我们发现 Cav2.2 通道的 KD 减少了小胶质细胞在黑质中的积累并改善了 PD 模型小鼠的行为缺陷。这些结果与在 Cav1.2 L 型通道的小胶质细胞特异性 KD 中发现的结果形成鲜明对比，其中观察到症状加重。我们的结果表明，阻断小胶质细胞 Cav2.2 N 型 VDCC 有利于 PD 的治疗。

更新日期：2020-06-16

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