1994 Fiscal Year Final Research Report Summary
Mechanism of Neuronal Cell Death following Cerebral Ischemia
| Project/Area Number |
05404049
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | University of Tokyo |
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Principal Investigator |
KIRINO Takaaki University of Tokyo, Facultiy of Medicine, Department of Nerosurgery, Professor, 医学部(病), 教授 (90126045)
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| Co-Investigator(Kenkyū-buntansha) |
MORIKAWA Eiharu University of Tokyo, Faculty of Medicine, Department of Nerosurgery, Assistant, 医学部(病), 助手 (90251256)
MORIMOTO Tadashi University of Tokyo, Faculty of Medicine, Department of Nerosurgery, Assistant, 医学部(病), 助手 (20230154)
SASAKI Tomio University of Tokyo, Faculty of Medicine, Department of Nerosurgery, Associate P, 医学部(病), 助教授 (10134561)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Cerebral ischemia / Cell daeth / Hippocampus / Mongolian gerbil / Stress protein / Protein synthesis / Ubiquitin / Synapse |
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| Research Abstract |
Neurons in the hippocampal CA1 sector die following brief period of ischemia. The neuronal injury here is almost purely postsynaptic. The long term change in remaining presynaptic terminals was studied by fine structural morphometry. The terminals were chronically maintained for longer than 3 months and gradually decreased in number. The CA1 region fell in atrophy in accordance with disappearance of residual presynaptic terminals. Brief ischemia, which in itself is not lethal to hippocampal neurons, confer tolerance to further ischemia even if the ischemic insult is lethal to neurons in intact condition. In neurons which have acquired ischemic tolerance, a stress protein, hsp70, is strongly expressed. We studied the change in protein synthesis in tolerance-induced neurons by autoradiography. Following ischemia, protein synthesis is severely inhibited in Ca1 and never recovers. On the other hand, in tolerance-induced animals, the recovery of protein synthesis was rapid even if ischemia was of lethal level. The change in mRNA for hsp70 was studied by in situ hybridization method. The message was always expressed in CA1 neurons even if the neurons were going to die. Following tolerance induction, mRNA expression was followed by intense expression of hsp70 protein. Another stress-inducible protein, ubiquitin, was known to disappear in CA1 neurons following ischemia. However, this was not the case when we used another type of anti-ubiquitin antibody which recognize mainly conjugated form of ubiquitin. Immunoblot and immunoprecipitation study revealed that uniqutin does not decrease in total amount but free form of ubiquitin is depleted from the CA1 neurons following ischemia. The role of the disappearance of free ubiquitin in ischemic neuronal death is still unknown.
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