RRC ID 57849
Author Wang X, Saegusa H, Huntula S, Tanabe T.
Title Blockade of microglial Cav1.2 Ca2+ channel exacerbates the symptoms in a Parkinson's disease model.
Journal Sci Rep
Abstract 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 the neuroinflammatory M1 transition and inhibited neuroprotective M2 transition of microglia in 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.
Volume 9(1)
Pages 9138
Published 2019-6-24
DOI 10.1038/s41598-019-45681-3
PII 10.1038/s41598-019-45681-3
PMID 31235768
PMC PMC6591481
MeSH Animals Biomarkers / metabolism Calcium Channels, L-Type / deficiency* Calcium Channels, L-Type / genetics* Disease Models, Animal Dopaminergic Neurons / pathology Gene Knockdown Techniques* Mice Microglia / metabolism* Microglia / pathology Parkinson Disease / genetics* Parkinson Disease / metabolism Parkinson Disease / pathology*
IF 3.998
Times Cited 3
Resource
Human and Animal Cells MG6(RCB2403)