2000 Fiscal Year Final Research Report Summary
Production of post-mitotic neurons expressing Amyloid precursor protein and analysis of their degenerative process
| Project/Area Number |
09670099
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General pharmacology
|
|---|
| Research Institution | Asahikawa Medicine College (1998-2000)
Nagano College of Nursing (1997) |
|---|
Principal Investigator |
HAYASHI Yokichi Asashikawa Medical College, Department of Life Sicence, Professsor, 医学部, 教授 (70173044)
|
|---|
| Project Period (FY) |
1997 – 2000
|
| Keywords | Adenovirus / Neuronal death / APP / IL-8 |
|---|
| Research Abstract |
When primary cultured neurons from rat hippocampus were infected with adenovirus vector expressing a gene encoding amyloid precursor protein (APP), they were gradually degenerated and died within 4-5 days. During this degeneration process, transient activation of caspase 3 was observed. Inhibition of this caspase by a peptide inhibitor resulted into a delay of neuronal death. In the case of glial cells, similar infection did not induce cellular death at all, however reactive oxygens were produced much more in infected glial cells than in uninfected ones. To clone novel genes related to the degeneration process in vitro, differential display method was employed. Only one clone was identified and turned out to be a fragment of cDNA coding for an IL-8. In the presence of IL-8, neuronal survival did not affected at all, whereas neuronal death was enhanced when APP gene was introduced simultaneously. These data, taken together, suggest that in this cellular model for sporadic Alzheimer' disease, neuronal death is mediated by cellular accumulation of APP fragments, but not by extracellular action of amyloid beta protein. Thus, this model system is very useful in view points of screening for anti-dementia foods or therapeutic chemicals for Alzheimer' disease, as well as of elucidation underling molecular mechanism of Alzheimer' disease.
|
