論文 - 詳細
| RRC ID | 57883 |
|---|---|
| 著者 | Huntula S, Saegusa H, Wang X, Zong S, Tanabe T. |
| タイトル | Involvement of N-type Ca2+ channel in microglial activation and its implications to aging-induced exaggerated cytokine response. |
| ジャーナル | Cell Calcium |
| Abstract |
Voltage-dependent calcium channel (VDCC) is generally believed to be active only in excitable cells. However, we have reported recently that N-type VDCC (Cav2.2) could become functional in non-excitable cells under pathological conditions. In the present study, we show that Cav2.2 channels are also functional in physiological microglial activation process. By using a mouse microglial cell line (MG6), we examined the effects of a Cav2.2 blocker on the activation of MG6 cells, when treated with lipopolysaccharide (LPS) / interferon γ (IFNγ) or with interleukin-4 (IL-4). As a result, blocking the activation of Cav2.2 enhanced so-called alternative activation process of microglia (transition to neuroprotective M2 microglia) without changing the efficacy of the transition to neuroinflammatory M1 microglia. This enhanced M2 transition involved the activation of a transcription factor hypoxia inducible factor 2 (HIF-2), since a specific blocker of HIF-2 completely abolished this enhancement. We then examined whether Cav2.2 activation was involved in aging-related neuroinflammation. Using primary culture of microglia, we found that the efficacy of microglial M1 transition was enhanced but that M2 transition was reduced by aging, in agreement with a general notion that aging induces enhanced neuroinflammation. Finally, we show here that the moderate blockade of Cav2.2 expression in microglia restores this age-dependent reduction of microglial M2 transition and reduces the aging-induced exaggerated cytokine response, as revealed by a fast recovery from depressive-like behaviors in microglia-specific Cav2.2 deficient mice. These results suggest a critical role for microglial Cav2.2 channel in the aging-related neuroinflammation. |
| 巻・号 | 82 |
| ページ | 102059 |
| 公開日 | 2019-9-1 |
| DOI | 10.1016/j.ceca.2019.102059 |
| PII | S0143-4160(19)30126-5 |
| PMID | 31377554 |
| MeSH | Aging / physiology* Animals Calcium Channels, N-Type / metabolism* Cell Line Immunity Interferon-gamma / metabolism Interleukin-4 / metabolism Lipopolysaccharides / immunology Mice Mice, Inbred C57BL Microglia / physiology* Neurogenic Inflammation / metabolism* Neuroprotection Signal Transduction Transcription Factors / genetics Transcription Factors / metabolism |
| IF | 4.874 |
| 引用数 | 1 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MG6(RCB2403) |