1995 Fiscal Year Final Research Report Summary
The study on crosstalk failure in the nervous system.
| Project/Area Number |
06044166
|
|---|
| Research Category |
Grant-in-Aid for international Scientific Research
|
| Allocation Type | Single-year Grants |
|---|
| Section | Joint Research |
|---|
| Research Institution | The Kagawa Medical School |
|---|
Principal Investigator |
HATASE Osamu The Kagawa Medical School・Professor, 医学部, 教授 (50033220)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
WAISMAN David m The University of Calgary・Professor, 医学部, 教授
WANG Jerry h The University of Calgary・Professor, 医学部, 教授
TOKUDA Masaaki The Kagawa Medical School・Associate Professor, 医学部, 助教授 (10163974)
ITANO Toshifumi The Kagawa Medical School・Associate Professor, 医学部, 助教授 (60145042)
MATSUI Hideki The University of Okayama・Professor, 医学部, 教授 (30157234)
NAKAHARA Sukita The Kagawa Medical School・Professor, 医学部, 教授 (70033024)
NAKANO Misao The Kagawa Medical School・Professor, 医学部, 教授 (20227862)
SUWAKI Hiroshi The Kagawa Medical School・Professor, 医学部, 教授 (10033367)
KONISHI Ryoji The Kagawa Medical School・Visiting Professor, 医学部, 客員教授
|
|---|
| Project Period (FY) |
1994 – 1995
|
| Keywords | intracellular signal transduction / crosstalk / epilepsy / Alzheimer's disease / plasticity / calmodulin-dependent kinases / Cdk 5 / p35 / Tau protein |
|---|
| Research Abstract |
The involvement of calmodulin dependent protein kinases (CaM-kinases) and cyclin-dependent kinase 5 (Cdk 5) in epilepsy and Alzheimer's disease was studied.
Among CaM-kinases known, CaM-kinase II has been demonstrated to play an important role in the plasticity of neuronal cells. We investigatd the possible involvement of CaM-kinase I and CaM-kinase IV in the neuronal plasticity during epileptogenesis. Amygdaloid-kindled rat brain was used for immunohistochemical study, Western blot analysis, Northern blot analysis and in situ hybridization study.
CaM-kinases I and IV were present in the control normal rat brain. Significantly incerased levels of both kinases were detected in the kindled cerebrum, while no obvious change was detected in cerebellum. Cdk 5 showed almost constant expression level in all stages of epileptogenesis. On the other hand, p35, a brain specific activator of Cdk 5, showed a significant increase at stage 3 where new synapse formation is most frequently observed. The level of p35 in other stages (stages 1,2,4, and 5) remained low. When the activity of Cdk 5/p35 was measured, the highest activity was detected at stage 3.
Tau protein has been known to be heavily phosphorylated in Alzheimer's brain and was found in paired helical tangles. We therefore checked if Tau was phosphorylated during epileptogenesis. Western blot analysis using an antibody against phosphorylated-Tau (p-Tau) demonstrated the high level of p-Tau presented at stage 3, while a lot less level of p-Tau in other stages. Western blot analysis using an antibody against nonphosphorylated-Tau showed a mirror image of that of p-Tau. We also demonstrated that both p-Tau and Cdk 5/p35 colocalized in Alzheimer's deposit.
These results together indicated that CaM-kinases and Cdk 5/p35 might play an pathogenic role in epileptogenesis and Alzheimer's disease.
|
