Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
FEBS Lett. 2020 Sep;594(17):2914-2922. doi: 10.1002/1873-3468.13853. Epub 2020 Jun 16.
Cav2.2 N-type voltage-dependent Ca 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.
神经元表达的 Cav2.2 型电压依赖性钙通道（VDCC）已知对神经递质释放至关重要。我们之前已经表明，这种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，我们在帕金森病（PD）的小鼠模型中检查了 Cav2.2 通道的小胶质细胞特异性敲低（KD）的影响。我们发现 Cav2.2 通道的 KD 减少了黑质中小胶质细胞的积累，并改善了 PD 模型小鼠的行为缺陷。这些结果与 Cav1.2 L 型通道的小胶质细胞特异性 KD 中观察到的结果形成鲜明对比，在后者中观察到症状加剧。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。
