Project/Area Number |
02304045
|
Research Category |
Grant-in-Aid for Co-operative Research (A)
|
Allocation Type | Single-year Grants |
Research Field |
Psychiatric science
|
Research Institution | Okayama University |
Principal Investigator |
MORI Akitane Okayama Univ. Med. Sch., Professor, 医学部, 教授 (20028434)
|
Co-Investigator(Kenkyū-buntansha) |
MIZIKAWA Kiminao Okayama Univ. Med. Sch., Assistant Professor, 医学部, 講師 (40137154)
SUZUKI Jiro Toho Univ. Sch. of Med., Professor, 医学部, 教授 (10090408)
SUGAYA Eiichi Kanagawa Dental Univ., Professor, 歯学部, 教授 (50084710)
YAMAGAMI Sakae Osaka Univ. Med. Sch., Associate Professor, 医学部, 助教授 (20047004)
MITA Takashi Univ. of Occupation and Environmental Health Sch. of Med., Professor, 医学部, 教授 (20076988)
|
Project Period (FY) |
1990 – 1991
|
Project Status |
Completed (Fiscal Year 1991)
|
Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1991: ¥3,000,000 (Direct Cost: ¥3,000,000)
|
Keywords | 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 |
Research Abstract |
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.
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