2001 Fiscal Year Final Research Report Summary
A study of a role for inducible GLP-1 in brain disfunctions
| Project/Area Number |
12672131
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | Tokyo University of Science |
|---|
Principal Investigator |
JUN-LCHIRO Oka Tokyo University of Science Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (40134613)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Keywords | β-Amyloid orotein / GLP-1 / Long-term potentiation(LTP) / Hippocampus / cAMP / MAP kinase / Primary culture / Neurite elongation |
|---|
| Research Abstract |
The final goal of the present study is to examine intracellular mechanisms of interaction between β-amyloid protein and glucagon-like peptide-1 (GLP-1) in progression of the brain dysfunction, and to examine a physiological role of GLP-1 in the brain development. First, we found that progression of apoptosis is an important factor for NFikB activation by p-amyloid protein, and that NFicB activation might not play a functional role in the interaction between p-amyloid protein and GLP-1.Next, we demonstrated that endogenous GLP-1 exacerbates p-amyloid protein-induced impairment of long-term potentiation in the hippocampal CA1 through CAMP-independent mechanism, and that activation of p38 MAP kinase may be involved in p-amyloid protein-induced dysfunction of synaptic plasticity and the interaction with GLP-1.Furthermore, we found that the presence of constitutive GLP-1 in the embryonic but not postnatal rat's hippocampus, where synthesis of GLP-1 is usually suppressed but is stimulated by treatment with p-amyloid protein. Cultured hippocampal neurons had GLP-1 receptors, and an antagonist of GLP-1 receptors inhibited neurite elongation without any effect on cell viability. Our results demonstrated that an increase in CAMP concentration and activation of MAP kinase pathways are involved in the effects of endogenous GLP-1.The same effects were also observed in cultured cerebrocortical neurons and cultured spinal neurons. These results suggest that endogenous GLP-1 acts as a neurotrophic factor in the brain of rat embryos, and that GLP-1 might show a therapeutic effect on the damaged brain by facilitating neurite elongation and re-organizing neuronal networks.
|
Research Products
(8 results)
-
-
-
-
-
-
[Publications] Hicks, T. P., Krasteniakov, N. V., Jackson, M, Donnelly, S. M., Chakravarthy, B, , Ohannessian, L, and Oka, J.-I.: "Altered electrophysiological expression of synapuc plasticity and infrared spectroscopic tissue composition in long-term β -amyl oid-treated rats."Acta Medica et Biologica. 48. 31-38 (2000)
Description
「研究成果報告書概要(欧文)」より
-
-
[Publications] Hashimoto, M., Hossain, Md. S., Shimada, T., Sugioka, K., Yamasaki, H., Fujii, Y., Ishibashi, Y., Oka, J.-I. and Shido, O: "Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer' s disease model rat"Journal of Neurochemistry. (in press). (2002)
Description
「研究成果報告書概要(欧文)」より
