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Epilepsy, Headache, Vertigo

開催日 2014/9/11
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Evaluation of the Lgi1L385R/+ rat as ADLTE model

  • P1-349
  • 麓 直浩 / Naohiro Fumoto:1,2,3 真下 知士 / Tomoji Mashimo:3 増井 淳 / Atsushi Masui:4 石田 紗恵子 / Saeko Ishida:3 水口 祐登 / Yuto Mizuguchi:4 南本 翔子 / Shoko Minamimoto:4 池田 昭夫 / Akio Ikeda:2,5 高橋 良輔 / Ryosuke Takahashi:2 芹川 忠夫 / Tadao Serikawa:3,4 大野 行弘 / Yukihiro Ohno:4 
  • 1:独立行政法人国立病院機構南岡山医療センター神経内科 / Dept Neurol, Minami-Okayama Med Ctr, Hayashima, Japan 2:京都大院医臨床神経 / Dept Neurol, Grad Med, Univ of Kyoto, Kyoto, Japan 3:京都大院医動物実験施設 / Inst Lab Animals, Grad Med, Univ of Kyoto, Kyoto, Japan 4:大阪薬科大薬品作用解析 / Lab Pharmacol, Osaka Univ of Pharm Sci, Takatsuki, Japan 5:京都大院医てんかん・運動異常生理 / Dept Epilepsy, Movement Disorders and Physiol, Grad Med, Univ of Kyoto, Kyoto, Japan 

Mutations in the leucine-rich, glioma inactivated 1 (Lgi1) gene have been identified in patients with autosomal dominant lateral temporal lobe epilepsy (ADLTE). We previously reported about Lgi1 mutant rats, carrying a missense mutation (L385R), generated by gene-driven N-ethyl-N-nitrosourea (ENU) mutagenesis. LGI1 protein secretion in the mutant rats was inhibited as the same as in the majority of ADLTE patients. Lgi1heterozygous mutant rats (Lgi1L385R/+) showed generalized tonic-clonic seizures (GTCS) in response to acoustic stimuli (Baulac S et al., 2012). In the present study, we further assessed Lgi1L385R/+ rats as an animal model of ADLTE.
In Lgi1L385R/+ rats, we performed electroencephalography (EEG) and brain Fos immunohistochemistry to explore the focus of the audiogenic seizures, and microarray analysis to find genes showing expression changes after GTCS. Ictal EEG showed bilateral rhythmic delta activities and rhythmic spikes in Lgi1L385R/+ rats while interictal EEG showed no abnormality. An elevated level of Fos expression indicated greater neural excitability to acoustic stimuli in Lgi1L385R/+ rats, especially in the temporal lobe, thalamus etc. Microarray analysis revealed some genes that showed expression changes after GTCS and may be involved in epilepsy.
The normal findings in interictal EEG and the focus revealed by Fos expression are consistent with those in ADLTE patients. Seizure-related genes identified in microarray analysis may be responsible for audiogenic seizures. We propose that Lgi1L385R/+ rats are a highly appropriate model for ADLTE, and results in this study can be clues of the seizure onset mechanism.

There is no conflict of interest with any financial organization regarding this study.

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