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Research for the Involvement of Noradrenergic System in the Seizures of Epileptic El Mice

去甲肾上腺素能系统参与癫痫小鼠癫痫发作的研究

基本信息

批准号：
63570435
负责人：
ITO Masatoshi
金额：
$ 1.34万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1990
项目状态：
已结题

项目摘要

To elucidate the role of noradrenergic system in the seizures of epileptic E1 mice, we tested the anticonvulsant effects of various drugs. We also quantitated adrenergic receptors, noradrenaline (NA), dopamine (DA) and cyclic-AMP (cAMP).in the whole brains and regional brains of the stimulated and unstimulated E1 mice, and their maternal ddY mice. Obtained results are as followings;1) NAergic system in the brains of E1 mice seemed to play a inhibitory bole on the seizures of the E1 mice. This inhibition seemed to be mediated by activations of alpha_1 - and alpha_2- adrenoceptors.2) Up-regulations of alpha_1-adrenoceptors in the striatum and cerebellum, alpha_2-adrenoceptors in the cerebral cortex, hippocampus and brainstem were observed in the stimulated and unstimulated E1 mice.3) Decreases of NA contents were observed in the striatum, hippocampus and frontal cortex of the stimulated E1 mice. These decrebtses became to be observed when mice were getting seizure susceptibility.4) From the results of NA turnover and time-dependent change of NA contents after seizures, hyperfunction of NAergic neurons in the hippocampus and hyperfunction of those in the striatum were suggested. Therefore, the manner of inhibition for seizured by NA- ergic system was different by brain regions, and this difference may be closely related the seizure susceptibility of the E1 mice.5) In the cerebral cortex of the stimulated E1 mice, c-AMP concentrations were decreased. After seizures, c-AMP contents increased in all of the brain regions except for hippocampus.

为了阐明去甲肾上腺素能系统在癫痫E1小鼠发作中的作用，我们测试了各种药物的抗惊厥作用。我们还定量了肾上腺素能受体、去甲肾上腺素（NA）、多巴胺（DA）和环amp （cAMP）。在受刺激和未受刺激的E1小鼠及其母系ddY小鼠的全脑和局部脑中均可见。所得结果如下：1) E1小鼠的脑能系统似乎对E1小鼠的癫痫发作起抑制作用。这种抑制似乎是由α 1 -和α 2-肾上腺素受体的激活介导的。2)刺激和未刺激E1小鼠纹状体、小脑、大脑皮层、海马和脑干的α _1-肾上腺素受体均上调。3)刺激E1小鼠纹状体、海马和额叶皮层NA含量降低。当小鼠变得癫痫易感性时，就可以观察到这些衰退。4)癫痫发作后NA转换和NA含量随时间变化的结果提示海马NA能神经元功能亢进，纹状体NA能神经元功能亢进。因此，不同脑区NA-能系统对癫痫发作的抑制方式不同，这种差异可能与E1小鼠的癫痫发作易感性密切相关。5)刺激E1小鼠大脑皮层c-AMP浓度降低。癫痫发作后，除海马外，所有脑区c-AMP含量均升高。