Knockdown of microglial Cav2.2 N-type voltage-dependent Ca channel ameliorates behavioral deficits in a mouse model of Parkinson's disease.

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.