INVESTTGATON OF FACTORS PROMOTING HIPPOCAMPAL SCLEROSIS IN THE MOUSE MODEL OF PROGRESSIVE HYPERTROPHY OF DENTATE GYRUS IN HIPPOCAMPUS.
| Project/Area Number |
13671432
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
SUZUKI Fumio SHIGA UNIVERSITY OF MEDICAL SCIENCE, MEDICAL SCHOOL, INSTRUCTOR, 医学部, 講師 (80171247)
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| Co-Investigator(Kenkyū-buntansha) |
KUROKAWA Kiyoshi SHIGA UNIVERSITY OF MEDICAL SCIENCE, MEDICAL SCHOOL, ASSISTANT PROFESSOR, 助教授 (40215083)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | HIPPOCAMPAL SCLEROSIS / AMPA / KA RECEPTORS / NMDA RECEPTOR / ANTAGONISTS / CULTURE / PROTEIN EXTRACTS / EPILEPSY / Flamingo / Celsr2 / 神経幹細胞 / 神経移植 / てんかんモデル / 細胞外液 / Hippocampus / granule cell / dispersion / glutumate receptor / AMPA / アンタゴニスト |
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| Research Abstract |
Single injection of small amount of kainic acid (KA) into mouse hippocampus induces the progressive dispersion and the enlargement of hippocampal granule cells that starts from 4days and lasts till 8weeks after KA injection. In this study, we investigated whether the factors that affect neuronal differentiations are involved or not in the KA injected hippocampus.
1, The results of culture studies: At 7 days after KA injection, protein extracts and extracellular fluid (ECF) of the dispersed hippocampus were collected. These two kinds of samples were added to the culture medium of neuronal stem cells or hippocampal slices. Adding the protein extract from the KA injected hippocampus onto slice hippocampal culture induced the neuronal cell degeneration of pyramidal cells of Ammon's horn. The neuronal stem cells did not influenced their differentiation to neuron or glia either by protein extracts or ECF of KA injected hippocampus. Since the ECF did not induce any difference from the artifici
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al cerebrospinal fluid, which is a vehicle to collect the ECF, the concentration of ECF was thought to be very low. Essentially ECF is more important than whole cell protein extracts to examine the environmental factors. However it might be quite difficult to collect enough amount of ECF for this experiment from mouse hippocampus. Another animals or method will be needed for future studies.
2: As mentioned above (1), protein extract showed some neurotoxicity to pyramidal cells of slice cultured hippocampus. This neurotoxicity was supposed to relate to glutamate or their related substances since the animals have been known to develop epilepsy. And their over-expression might be a cause of granule cell dispersion. To examine this hypothesis the antagonists of glutamate were administrated and the changes of dentate gyros were examined. And we found that the activation of NMDA receptor regulates the development of the dispersion. This result was submitted to Epilepsia.
3: We investigated the mRNA, which were expressed specifically in dispersed hippocampus, by differential display method as an theme of the previous Grant-in-Aid for Scientific Research ( C ). Flamingo/Celsr2 was identified as one of the candidate gene that might be related to the dispersion, and the result was reported in Brain Research. Less
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Report
(4 results)
Research Products
(4 results)
