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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)

Analysis of brain regions responsible for nicotine-induced convulsions

  • P1-353
  • 國澤 直史 / Naofumi Kunisawa:1 清水 佐紀 / Saki Shimizu:1 水口 裕登 / Yuto Mizuguchi:1 奥村 貴裕 / Takahiro Okumura:1 徳留 健太郎 / Kentaro Tokudome:1 大高 美幸 / Miyuki Ohtaka:1 近持 壽郎 / Hisao Chikamochi:1 高久保 佑一 / Yuichi Takakubo:1 芹川 忠夫 / Tadao Serikawa:1 大野 行弘 / Yukihiro Ohno:1 
  • 1:大阪薬大・薬・薬品作用解析 / Lab. Pharmacol., Osaka Univ. Pharm. Sci, Osaka. Japan 

Nicotine at high doses elicits convulsive seizures. In addition, mutations of nicotinic acetylcholine (nACh) receptors induce Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE) in human, suggesting that nACh receptors are involved in epileptic disorders. In this study, we analyzed the brain expression of Fos protein, a biological marker of neural excitation, in mice to clarify the causative regions involved in nicotine-induced convulsions. Male ddY mice were given with nicotine (4 mg/kg, i.p.) and the incidence of convulsive seizures were monitored for 15 min. Brains were then removed from the skull 2 hours after the nicotine injection and subjected to Fos-immunohistochemistry. Intraperitoneal injection of nicotine (4 mg/kg) induced motor excitation, such as straub tail and tremor, and consequently tonic-clonic convulsions. Nicotine-induced convulsions occurred transiently and recovered within 10 min. The non-selective nACh antagonist mecamylamine and the α7-nACh antagonist methyllycaconitine significantly inhibited nicotine-induced convulsions while the α4-nACh antagonist dihydro-β-erythroidine showed no effects. Brain mapping analysis of Fos protein expression revealed that nicotine region-specifically elevated Fos protein expressiopn in the agranular insular cortex (AIC), piriform cortex (Pir), amygdala (AMG), medial habenular nucleus (MHb), some parts of thalamus (Th) and hypothalamus (HT), and solitary nucleus (Sol). However, other brain regions such as hippocampus and basal ganglia were unaffected with nicotine. In addition, mecamylamine significantly reversed the nicotine-induced elevation of Fos expression in most of the above brain regions. Taken together with the observation that subconvulsive doses of nicotine (1 mg/kg) elevate Fos expression in the MHb, Th, HT and Sol, the present study suggest that nicotine evokes convulsive seizures by activating the Pir and/or AMG at least partly through α7 nACh receptors.

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