Analysis of the protective effects of the α2/δ subunit of voltage-gated Ca2+ channels in brain injury

Tae Yeon Kim, Kimie Niimi, Eiki Takahashi

研究成果: Contribution to journalArticle査読

2 被引用数 (Scopus)

抄録

Voltage-gated Ca2+ channels (VGCCs) are comprised of α1, α2/δ, β, and γ subunits. The pore-forming α1 subunit is essential for the proper functioning of Ca2+ channels, while the α2/δ subunit interacts with components of the extracellular matrix. The α2/δ subunit is related in many neuropathological symptoms, including epilepsy and cerebellar ataxia. We previously reported that the mutant Cav.2.1α1 subunit has protective effects following brain injury. The present study aimed to investigate the effects of the α2/δ subunit inhibition alone and in combination with the inhibition of the Cav.2.1α1 subunit following brain injury by injecting Gabapentin using Cav.2.1α1 mutant heterozygous rolling Nagoya (rol/+) and wild-type (+/+) mice. Gabapentin binds to the α2/δ subunit and leads to Ca2+ flow disturbance. A cryogenic method was used to induce brain injury. The mice pretreated with 100 mg/kg Gabapentin exhibited a decrease in lesion size, while the 40 mg/kg Gabapentin injection was effective in rol/+ mice but not +/+ mice. The administration of 100 mg/kg Gabapentin also attenuated reactive astrocyte activity and neuronal degeneration; the pattern of results was similar to that for lesion size. An analysis of phosphorylated p38 (pp38) expression revealed that Gabapentin suppressed the p38 mitogen-activated protein kinase (MAPK) signaling cascade by interrupting glutamate-signaling induced by the inhibition of VGCCs. The present findings demonstrated that the administration of the α2/δ subunit inhibitor, Gabapentin, had neuroprotective effects following brain injury.

本文言語英語
ページ(範囲)138-144
ページ数7
ジャーナルBrain Research
1655
DOI
出版ステータス出版済み - 1 15 2017
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経科学(全般)
  • 分子生物学
  • 臨床神経学
  • 発生生物学

フィンガープリント

「Analysis of the protective effects of the α<sub>2</sub>/δ subunit of voltage-gated Ca<sup>2+</sup> channels in brain injury」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル