1998 Fiscal Year Final Research Report Summary
Regulation of neuronal plasticity by calmodulin dependent protein phosphatase, Calcineurin
| Project/Area Number |
08670053
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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 |
General physiology
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| Research Institution | Okayama University |
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Principal Investigator |
MATSUI Hideki Okayama University, Medical School, Professor, 医学部, 教授 (30157234)
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| Co-Investigator(Kenkyū-buntansha) |
TOMIZAWA Kazuhito Okayama University, Medical School, Assistant, 医学部, 助手 (40274287)
MATSUSHITA Masayuki Okayama University, Medical School, Assistant, 医学部, 助手 (30273965)
MORIWAKI Akiyoshi Okayama University, Medical School, Associate Professor, 医学部, 講師 (10144742)
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| Project Period (FY) |
1996 – 1998
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| Keywords | calcineurin / FK506 / Cyclosporin A / LTP / LTD / Voltage dependent calcium channel / Kainate / Delayed neuronal cell death |
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| Research Abstract |
The signals conveyed by intracellular Ca^<+2> ion concentration distribute into kinase system and phosphatase system, and express their physiological functions by controlling the phosphorylation level of target proteins. Calcineurin is a sole protein phosphatase which is directly regulated by Ca^<+2> and calmodulin and thus it is a key enzyme transmitting and amplifying signals by regulating serine/threonine phosphatase cascade. Calcineurin is extremely abundant in brain and co-localizes with FKBP12(FK506 binding protein 12) and cyclophilin(Cyclosporin A binding protein). Thus the immunosuppressants FK506 and Cyclosporin A(CysA) can specifically inhibits calcineurin activity.
In this research project, we analysed the physiological role of calcineurin in central nervous system by the usage of FK506 and CysA as specific inhibitors. We specifically stressed the points as follows :
1. The role of calcineurin in the control of synaptic plasticity of hippocampal neurons
2. Calcineurin involvement in the acquisition of epileptogenesis induced by electrical kindling and morphological plasticity such as neuronal process extension and synaptogenesis observed in kindling.
3. The role of calcineurin in the control mechanism of delayed neuronal cell death in hippocampal CA1 pyramidal neuron.
4. The neuroprotection activity of FK506 in delayed neuronal cell death.
We showed that calcineurin controls neuronal process formation, synaptogenesis and neuron network formation. The enzyme further controls the synapse plasticity such as LTP and LTD by modulating the NMDA channel and voltage -dependent calcium channel. Calcineurin has essential role in controlling the apoptosis of neurons and so the inhibitor of calcineurin, FK506 inhibits the neuronal apoptosis and works as neuro-protector.
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