Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8478596 | Molecular and Cellular Neuroscience | 2015 | 12 Pages |
Abstract
Under pathological conditions, microglia, the resident CNS immune cells, become reactive and release pro-inflammatory cytokines and neurotoxic factors. We investigated whether this phenotypic switch includes changes in the expression of the L-type voltage-gated calcium channel (VGCC) in a rat model of N-methyl-d-aspartate-induced hippocampal neurodegeneration. Double immunohistochemistry and confocal microscopy evidenced that activated microglia express the L-type VGCC. We then analyzed whether BV2 microglia express functional L-type VGCC, and investigated the latter's role in microglial cytokine release and phagocytic capacity. Activated BV2 microglia express the CaV1.2 and CaV1.3 subunits of the L-type VGCC determined by reverse transcription-polymerase chain reaction, Western blot and immunocytochemistry. Depolarization with KCl induced a Ca2+ entry facilitated by Bay k8644 and partially blocked with nifedipine, which also reduced TNF-α and NO release by 40%. However, no nifedipine effect on BV2 microglia viability or phagocytic capacity was observed. Our results suggest that in CNS inflammatory processes, the L-type VGCC plays a specific role in the control of microglial secretory activity.
Keywords
DABMDPIFNγIB4N-methyl-d-aspartateNMDAIL-1βNGSGFAPLSDPBSLPSFBS[Ca2+]iNeuroinflammationexcitotoxicityisolectin B4interferon-gammaInterleukin-1βNeurodegenerationtumor necrosis factor alphaleast significant differencestandard error of the meandiaminobenzidinefetal bovine serumnormal goat serumdentate gyrusintracellular calcium concentrationTNF-αphosphate buffer salinelipopolysaccharideSEMGlial fibrillary acidic proteinL-type voltage-gated calcium channeldihydropyridine receptor
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Authors
J.F. Espinosa-Parrilla, M. MartÃnez-Moreno, X. Gasull, N. Mahy, M.J. RodrÃguez,