| Project/Area Number |
17591652
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Anesthesiology/Resuscitation studies
|
|---|
| Research Institution | Tokyo Medical University |
|---|
Principal Investigator |
MATSUMOTO Shohei Tokyo Medical University, Medicine, lecturer, 医学部, 講師 (30256250)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MUROZONO Michihiro Tokyo Medical University, Medicine, lecturer, 医学部, 講師 (70276947)
WATANABE Yasuo Nippon Pharmacology University, Pharmacology, professor, 薬学部, 教授 (70183720)
ISSHIKI Atsushi Tokyo Medical University, Medicine, professor, 医学部, 教授 (60074796)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | inhalation anesthetics / CaMKII / immuno-precipitation / neuroprotecition / NMDA / NR2 / phospho-tyrosine / 免疫沈降 / NMDAレセプター / チロシンリン酸化 / イソフルレン |
|---|
| Research Abstract |
Male C57/Black mice were decapitated after inhalation of isoflurane or sevoflurane, and N-methyl-D-aspartate (NMDA) receptor subunits NR2A, NR2B were measured. The interaction between these subunits and calcium-calmodulin dependent protein kinase II (CaMKII) was also measured. Immuno-precipitation and western blot analysis were used for these studies.
Method : Mice ischemia model was made by decapitation. After decapitation, the skull was incubated in the 37℃ saline 3 or 5 min, then stored-80℃. Previous to the decapitation, 1MAC or 2MAC isoflurane or sevoflurane were inhalated. The cerebrum was dissected from the skull in the cold globe box (-28℃), then homogenized. Using these samples immuno-precipitation was performed targeting to phosphor-tyrosine. Then the samples were assayed by SDS-PAGE, following western blot analysis was performed with anti-NR2A antibody and anti-NR2B antibody. Likewise, the interaction between phosphor-CaMKII and NR2A, B subunits were also examined.
Results : NR2A phosphorylation was decreased when isoflurane and sevoflurane inhalation. The change of NR2B was not obvious. There is a tendency that the change of NR2A phosphorylation is dozing dependent for inhalation anesthetics. The interaction between phosphor-CaMKII and NR2A. B subunits has not been evident so far.
Conclusion : Inhalation anesthetics prevent CaMKII translocation to synaptic membrane, subsequently the interaction between phosphor-CaMKII and NR2A is decreased, resulting down regulation of NR2A phosphorylation which reeds to neuroprotecition.
|
