THE ROLE OF NEURON-SPECIFIC PROTEASE, NEUROPSIN, IN THE DEVELOPMENT OF ISCHEMIC SYNAPTIC DYSFUNCTION
| Project/Area Number |
11670649
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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 |
Neurology
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| Research Institution | HYOGO COLLEGE OF MEDICINE |
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Principal Investigator |
MATSUYAMA Tomohiro HYOGO COLLEGE OF MEDICINE, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (10219529)
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| Co-Investigator(Kenkyū-buntansha) |
ISO Hiroyuki HYOGO COLLEGE OF MEDICINE, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (80068585)
SHIOSAKA Sadao NARA INSTITUTE OF SCIENCE AND TECHNOLOGY, DIVISION OF STRUCTURAL CELLULAR BIOLOGY, PROFESSOR, バイオサイエンス研究科, 教授 (90127233)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | NEUROPSIN / PROTEASE / CEREBRAL ISCHEMIA / KNOCK OUT MICE / LEARNING AND MEMORY / HIPPOCAMPUS |
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| Research Abstract |
Neuropsin is a limbic-specific serine protease involved in synaptic transmission and plasticity. Decrease in neuropsin content by in vivo infusion of an antisense DNA against neuropsin has reduced the amplitude of early phase of LTP in the hippocampus (1). Abnormalities of synapses and neurons was observed in the hippocampus of neuropsin-deficient mice (2). Effects of neuropsin deficiency on behavioral outcome have not been evaluated. We studied the role of neuropsin in cognitive function using mice deficient in neuropsin (3).
The total amount of locomotive activity (ambulating) was significantly greater in neuropsin-/- mice (p<0.005). The latency to find the hidden platform was significantly longer in neuropsin-/- mice than in neuropsin+/+ mice. Performance in the probe trial was not significantly different. Acquisition of visible platform task was similar in neuropsin+/+ and neuropsin -/- mice.
A transient 15-min ischemia (severe ischemia) caused delayed neuronal death in CA1 region, w
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hile 10-min ischemia (mild ischemia) did not cause cell death but induced tolerance in the CA1 neurons. Animals undergoing severe ischemia showed a higher locomotor activity judged by the open-field test, and a longer latencyjudged by the water-maze test than sham-operated animals. Mice undergoing mild ischemia also showed a significantly longer latency, indicating that these animals have an impairment of hippocampal function. In situ hybridization demonstrated that mild ischemia reduced the hybridization signals for neuropsin mRNA selectively in the CA1 region.
The present study clearly demonstrated that the ischemic insult induced neuronal dysfunction, even if the insult was not lethal to the neurons. It is very likely that such a dysfunction includes the lower expression of neuropsin in the CA1 neurons because its decrease or absence caused both synaptic and behavioral changes in mice. These findings suggest the important role of neuropsin in the functional prognosis of the ischemic stroke patients. Less
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Report
(3 results)
Research Products
(13 results)
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[Publications] Hirata A, Yoshida S, Inoue N, Matsumoto K, Ninomiya A, Taniguchi M,Matsuyama T, Kato K, Iizaka H, Kataoka Y, Yoshida N, Shiosaka S :: "Abnormalities of synapses and neurons in the hippocampus of neuropsin-deficient mice."Mol Cell Neurosci. (in press). (2001)
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