2002 Fiscal Year Final Research Report Summary
Research for the mechanism of ischemic tolerance in neuronal cells
| Project/Area Number |
13671446
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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 | Kumamoto University |
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Principal Investigator |
YANO Shigetoshi Kumamoto University School of Medicine, Department of Neurosurgery, Instructor, 医学部附属病院, 助手 (60332871)
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| Co-Investigator(Kenkyū-buntansha) |
GOTO Satoshi Kumamoto University School of Medicine, Department of Neurosurgery, Associate Professor, 医学部, 助教授 (50240916)
HAMADA Jun-ichiro Kumamoto University School of Medicine, Department of Neurosurgery, Assistant Professor, 医学部附属病院, 講師 (40253752)
USHIO Yukitaka Kumamoto University School of Medicine, Department of Neurosurgery, Professor, 医学部, 教授 (20028583)
MORIOKA Motohiro Kumamoto University School of Medicine, Department of Neurosurgery, Instructor, 医学部附属病院, 助手 (20295140)
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| Project Period (FY) |
2001 – 2002
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| Keywords | ISCHEMIC TOLERANCE / Akt / CREB / PHOSPHORYLATION / HIPPOCAMPUS / リン酸化反応 |
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| Research Abstract |
To investigate the mechanism of ischemic tolerance, we first focused on the activity of Akt that was reported as a key enzyme of anti-apoptotic signaling. Sublethal ischemia gradually and persistently activated Akt in hippocampal CA1 region. Intra-cerebral ventricular infusion of wortmannin prior to preconditioning blocked both the increase in Akt activation and the neuroprotective action of preconditioning. Next we examined the activation of CREB that was one of the candidates for the target of Akt signaling. Phosphorylation and binding activity of CREB after sublethal ischemia was observed transiently. Inhibition of CREB-DNA binding by infusion of CRE-decoy into the cerebral ventricle resulted in failure of induction of ischemic tolerance. These results suggested that Akt signaling and CREB activation contributed to neuroprotective ischemic tolerance in CA1 pyramidal neurons. As these effects could not explain the entire mechanism of ischemic tolerance, we are going to keep on investigating other key molecules.
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