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El mice : Seizure mechanisms and their management

El 小鼠：癫痫发作机制及其管理

基本信息

批准号：
02304045
负责人：
MORI Akitane
金额：
$ 1.92万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Co-operative Research (A)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02304045/
关键词：
El*mice Poly A^+ RNA c-fos mRNA Glutamic Aicd Aspartic Acid GABA Tyrosine serotonin トリプトファンシタロプラム mRNA異常発現 NMDAレセプタ-GABA作動系異常神経伝達物質 Ca輸送 baclofen

项目摘要

All experimental results by our research group are as follows :1. The amino acid metabolism and gene activity, including poly-A^+ RNA and sodium channel mRNA expression, were unusual at the early postnatal stage in the brain and liver.2. The expression of c-fos RNA was observed just after convulsion in the brain of seizure experienced El mice.3. Disturbances of neuronal growth, development and differentiation were observed. Excitatory state of neuronal membrane was detected without any convulsant in the primary curtured neuron.4. Mechanisms for onset of secondary generalized seizures were studied in the hippocampal neurons.5. Decreased cell numbers and dendrites, and also muscimol binding sites were observed in the hippocampal region.6. Epileptogenic abnormalities in the excitatory neurotransmitter binding sites were recognized.7. Disorders in the GABAergic, noradrenergic, and glutamateric receptors were found in the brain.8. GABAergic and glutamatergic neuronal systems changed with growth, development or stimulations.9. Abnormal release of excitatory and inhibitory neurotransmitters was observed in the cerebral and hippocampal slices.10. Genetically and extraordinally higher level of kynurenine, lower level of dopamine, and other metabolic disorders, were found in the brain.11. Decreased transport of Ca into blood from the bone was recognized. This decreased availability of Ca may result in a decrease of calmodulin dependent synthesis of amines, which leads to a lowered seizure threshold.12. El mouse seizures were inhibited by baclofen, a GABA_B receptor agonist, and citalopram, an inhibitor for serotonin re-uptake.13. El mouse strain has been controlled genetically and microbiologically to keep and to breed and also to be easy available to any epileptologists for further experiments.

本课题组的实验结果如下：1.在出生后早期，脑和肝脏的氨基酸代谢和基因活性，包括poly-A^+ RNA和钠通道mRNA的表达都不正常.癫痫发作小鼠惊厥后即刻脑内c-fos RNA表达明显增加.观察到神经元生长、发育和分化障碍。原代培养的神经元细胞膜呈兴奋状态，无惊厥剂作用.在海马神经元中研究继发性全身性发作的发病机制.海马区细胞数量和树突减少，蝇蕈醇结合位点也减少。兴奋性神经递质结合位点的致癫痫异常被识别。在大脑中发现GABA能、去甲肾上腺素能和多巴胺能受体的紊乱。GABA能和谷氨酸能神经元系统随生长、发育或刺激而改变.在大脑和海马切片中观察到兴奋性和抑制性神经递质的异常释放。遗传和非凡的水平较高的犬尿氨酸，较低水平的多巴胺，和其他代谢紊乱，被发现在大脑中。11.人们认识到钙从骨骼向血液的转运减少。这种Ca的可用性降低可能导致钙调素依赖性胺合成的减少，这导致癫痫发作阈值降低。GABA_B受体激动剂巴氯芬和5-羟色胺再摄取抑制剂西酞普兰可抑制El小鼠癫痫发作。El小鼠品系已被遗传和微生物学控制以保持和繁殖，并且也易于被任何癫痫学家用于进一步的实验。