【博士論文】学術データベース

博士論文 / Deletion of the BH3-only protein Noxa alters electrographic seizures but does not protect against hippocampal damage after status epilepticus in mice

書誌事項

タイトル

Deletion of the BH3-only protein Noxa alters electrographic seizures but does not protect against hippocampal damage after status epilepticus in mice

著者名

市川尚己

著者名

Ichikawa Naoki

学位授与大学

三重大学 (大学ID:0046) (CAT機関ID:KI000538)

取得学位

博士(医学)

学位授与番号

甲医学第1831号

学位授与年月日

2017-03-24

注記・抄録

Several members of the Bcl-2 gene family are dysregulated in human temporal lobe epilepsy and animal studies show that genetic deletion of some of these proteins influence electrographic seizure responses to chemoconvulsants and associated brain damage. The BH3-only proteins form a subgroup comprising direct activators of Bax-Bak that are potently proapoptotic and a number of weaker proapoptotic BH3-only proteins that act as sensitizers by neutralization of antiapoptotic Bcl-2 family members. Noxa was originally characterized as a weaker proapoptotic, 'sensitizer' BH3-only protein, although recent evidence suggests it too may be potently proapoptotic. Expression of Noxa is under p53 control, a known seizure activated pathway, although Noxa has been linked to energetic stress and autophagy. Here we characterized the response of Noxa to prolonged seizures and the phenotype of mice lacking Noxa. Status epilepticus induced by intra-amygdala kainic acid caused a rapid increase in expression of noxa in the damaged CA3 subfield of the hippocampus but not undamaged CA1 egion. In vivo upregulation of noxa was reduced by pifithrin-α, suggesting transcription may be partly p53-dependent. Mice lacking noxa developed less severe electrographic seizures during status epilepticus in the model but, surprisingly, displayed equivalent hippocampal damage to wild-type animals. The present findings indicate Noxa does not serve as a roapoptotic BH3-only protein during seizure-induced neuronal death in vivo. This study extends the comprehensive phenotyping of seizure and damage responses in mice lacking specific Bcl-2 gene family members and provides further evidence that these proteins may serve roles beyond control of cell death in the brain.

本文 / Department of Physiology & Medical Physics Royal College of Surgeons in Ireland; Department of Neurosurgery, Mie University Graduate School of Medicine

32p

内容の要旨・審査結果の要旨 / 三重大学大学院医学系研究科 生命医科学専攻 臨床医学系講座 脳神経外科学分野

キーワード

Apoptosis, Autophagy, Temporal lobe epilepsy, Epileptogenesis, Hippocampal sclerosis

各種コード

NII論文ID(NAID)

500001044315

NII著者ID(NRID)
  • 8000001153673
  • 8000001153674
DOI (出版社)

10.1038/cddis.2016.301

本文言語コード

eng

データ提供元

機関リポジトリ, NDLデジタルコレクション

外部リンク

博士論文 / 三重大学 / 医学

博士論文 / 三重大学

博士論文 / 医学

博士論文 / 大学

博士論文 / 学位