Age-dependent kainate sensitivity in heterozygous rolling Nagoya Cav2.1 channel mutant mice

Tae Yeon Kim, Takuro Yoshimoto, Yo Aoyama, Kimie Niimi, Eiki Takahashi, Chitoshi Itakura

研究成果: Contribution to journalArticle査読

5 被引用数 (Scopus)

抄録

Cav2.1α1 is involved in glutamate release. The kainate-induced intensive firing of neurons via glutamate receptors causes seizure and neuronal damage, especially in the hippocampus. Cav2. 1α1 mutation in homozygous rolling Nagoya (rol/rol) mice caused reduced Ca2 + permeability compared to wild-type mice. The rol/rol mice exhibited ataxia approximately after 2 weeks of age. Although we have reported that heterozygous rolling Nagoya (rol/+) mice show age-dependent behavioral changes, sensitivity to kainate has not been examined. To examine the relationship between Cav2.1 function and neurological disease, we investigated how Cav2.1 is related to kainate-induced seizure and neuronal damage using 2- and 18-month-old rol/+ mice. The seizure scores of 18-month-old rol/+ mice that received 20 mg/kg kainate intraperitoneally were significantly lower than those of wild-type mice. As a consequence of seizure, kainate induced delayed neuronal damage along with astrocytic growth in the hippocampus in wild-type mice, with a moderate effect observed in rol/+ mice. In the hippocampus of 18-month-old rol/+ mice, the levels of mutant-type Cav2.1α1 were increased compared to +/+ mice. The phosphorylation of p38, a mitogen-activated protein kinase (MAPK) activated by kainate, was not increased after kainate injection compared to +/+ mice. No difference was observed between 2-month-old rol/+ and wild-type mice intraperitoneally injected with 20 mg/kg kainate in these analyses. These findings suggest that rol/+ mice experience age-related changes in sensitivity to kainate due to changes in the p38 MAPK signaling pathway via a mutant Cav2.1 channel. Hence, rol/+ mice may represent a novel model to delineate the association between Cav2.1 function, synaptic transmission, and the postsynaptic signaling cascade.

本文言語英語
ページ(範囲)250-259
ページ数10
ジャーナルPharmacology Biochemistry and Behavior
124
DOI
出版ステータス出版済み - 9 2014
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学
  • 毒物学
  • 薬理学
  • 臨床生化学
  • 生物学的精神医学
  • 行動神経科学

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