A study of new therapeutic candidates for Alzheimer's disease utilizing microglia activation by
| Project/Area Number |
17590138
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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 |
Medical pharmacy
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
OKA Jun-Ichiro Tokyo University of Science, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (40134613)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | GLP-1 / microglia / astrocyte / IL-1β / GLT-1 / inflammation / excitotoxicity / neurodegenerative disease / アストログリア / cAMP / CREB / 認知症 |
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| Research Abstract |
In the early stage of Alzheimer's disease, neuroinflammation is considered to be important, and cytokines released from glia play a role in progression of the phenomena. Since lipopolysaccharide (LPS) could experimentally induce similar inflammatory changes in the brain, we examined the effects of glucagon-like peptide-1 (GLP-1) on LPS-induced cytokine expression in cultured astrocytes derived from the E18 rat's cortex. RT-PCR analysis showed that GLP-1 suppressed LPS-induced IL-β,IL-6 and iNOS expressions. Furthermore, ELISA demonstrated that peptide levels of IL-1β in the culture medium decreased in response to GLP-1 through the cAMP system and CREB phosphorylation. Furthermore, we investigated the effects of GLP-1 on the glial glutamate transporter, GLT-1, mRNA expression, since a decrease in glutamate transporters in Alzheimer's disease, and an inhibition of glutamate uptake into glia by (3-amyloid protein were reported, which phenomena may result in an increase in excitotoxicity by glutamate. GLP-1 treatment increased the GLT-1 mRNA expression in cultured astrocytes. We suggest that GLP-1 may protect neurons from excitotoxicity through an increase in glial glutamate transporters in the pathological conditions of the central nervous system. These results suggest that GLP-1 has neuroprotective effects through the inhibition of excitotoxicity as well as suppression of pro-inflammatory cytokines production after microglia activation.
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Report
(3 results)
Research Products
(4 results)
