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N-type calcium channel in the pathogenesis of experimental autoimmune encephalomyelitis.


ABSTRACT: One of the family of voltage-gated calcium channels (VGCC), the N-type Ca(2+) channel, is located predominantly in neurons and is associated with a variety of neuronal responses, including neurodegeneration. A precise mechanism for how the N-type Ca(2+) channel plays a role in neurodegenerative disease, however, is unknown. In this study, we immunized N-type Ca(2+) channel ?(1B)-deficient (?(1B)(-/-)) mice and their wild type (WT) littermates with myelin oligodendrocyte glycoprotein 35-55 and analyzed the progression of experimental autoimmune encephalomyelitis (EAE). The neurological symptoms of EAE in the ?(1B)(-/-) mice were less severe than in the WT mice. In conjunction with these results, sections of the spinal cord (SC) from ?(1B)(-/-) mice revealed a reduction in both leukocytic infiltration and demyelination compared with WT mice. No differences were observed in the delayed-type hypersensitivity response, spleen cell proliferation, or cytokine production from splenocytes between the two genotypes. On the other hand, Western blot array analysis and RT-PCR revealed that a typical increase in the expression of MCP-1 in the SC showed a good correlation with the infiltration of leukocytes into the SC. Likewise, immunohistochemical analysis showed that the predominant source of MCP-1 was activated microglia. The cytokine-induced production of MCP-1 in primary cultured microglia from WT mice was significantly higher than that from ?(1B)(-/-) mice and was significantly inhibited by a selective N-type Ca(2+) channel antagonist, ?-conotoxin GVIA or a withdrawal of extracellular Ca(2+). These results suggest that the N-type Ca(2+) channel is involved in the pathogenesis of EAE at least in part by regulating MCP-1 production by microglia.

SUBMITTER: Tokuhara N 

PROVIDER: S-EPMC2963360 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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N-type calcium channel in the pathogenesis of experimental autoimmune encephalomyelitis.

Tokuhara Naoki N   Namiki Kana K   Uesugi Mai M   Miyamoto Chihiro C   Ohgoh Makoto M   Ido Katsutoshi K   Yoshinaga Takashi T   Yamauchi Toshihiko T   Kuromitsu Junro J   Kimura Sadao S   Miyamoto Norimasa N   Kasuya Yoshitoshi Y  

The Journal of biological chemistry 20100818 43


One of the family of voltage-gated calcium channels (VGCC), the N-type Ca(2+) channel, is located predominantly in neurons and is associated with a variety of neuronal responses, including neurodegeneration. A precise mechanism for how the N-type Ca(2+) channel plays a role in neurodegenerative disease, however, is unknown. In this study, we immunized N-type Ca(2+) channel α(1B)-deficient (α(1B)(-/-)) mice and their wild type (WT) littermates with myelin oligodendrocyte glycoprotein 35-55 and an  ...[more]

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