Effect of Entorhinal Cortex on Hippocampal Neurotransmitter Function
| Project/Area Number |
11670970
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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 |
Psychiatric science
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
UEKI Akinori Hyogo College of Medicine, Department of Neuropsychiatry, Assistant Professor, 医学部, 講師 (30203425)
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| Co-Investigator(Kenkyū-buntansha) |
SHINJO Hidetaka Hyogo College of Medicine, Department of Neuropsychiatry, Research Associate, 医学部, 助手 (90330456)
MIWA Chitoku Hyogo College of Medicine, Department of Neuropsychiatry, Research Associate, 医学部, 助手 (60309458)
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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 |
¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1999: ¥400,000 (Direct Cost: ¥400,000)
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| Keywords | Alzheimer's disease / Entorhinal cortex / Hippocampus / Learning impairment / Brain microdialysis / Acetylcholine / Acetylcholinesterase / Synaptophysin / オペラント学習 / 動物モデル |
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| Research Abstract |
The entorhinal cortex is a primary supplier of converging neocortical sensory input into the hippocampal formation. In Alzheimer's disease, the entorhinal cortex is the earliest anatomical region to show neuropathological change. Because the structure of the entorhinal cortex is altered by the early degenerative processed associated with Alzheimer's disease, this area might be involved in aspects of memory processes that deteriorate with the disease. To explore for biochemical changes of the hippocampus associated with entorhinal cortex damage, we investigated changes in hippocampal cholinergic system and septal dopaminergic system of entorhinal cortex-lesioned rat during positive reinforcemrnt operant learning behavior using an in vivo microdialysis technique. This result suggested that entorhinal cortex lesion may cause damage to the hippocampal cholinergic system having no effect on the septal dopaminergic system with disruption of the entorhinal cortex-hippocampus relay passage. Moreover, we examined 12-week changes in histochemically demonstrated distribution of acetylcholinesterase and patterns of immunoreactivity for synaptophysin in the hippocampus following an entorhinal cortex lesion in rats. The present study revealed a loss of acetylcholinesterase-positive fibers and synaptophysin-immunoreactive presynaptic terminals in the hippocampus after an entorhinal cortex lesion, and the decrease of synaptophysin-immunoreactive presynaptic terminals progressed with time. These results demonstrated that entorhinal cortex lesion causes not only cholinergic dysfunction but also synaptic loss in the hippocampus. These findings offer support for the idea that the neuropathological change of the entorhinal cortex may be associated with momory deficit in Alzheimer's disease. Rats with entorhinal cortex lesion may be useful for constructing an animal model to study the pathophysiology of Alzheimer's disease and develop new strategies for its treatment.
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Report
(3 results)
Research Products
(9 results)
