A study of a role for inducible GLP-1 in brain disfunctions

诱导型 GLP-1 在脑功能障碍中的作用研究

基本信息

批准号：
12672131
负责人：
JUN-LCHIRO Oka
金额：
$ 2.18万
依托单位：
Tokyo University of Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672131/
关键词：
β-Amyloid orotein GLP-1 Long-term potentiation(LTP)Hippocampus cAMP MAP kinase Primary culture Neurite elongation GA1 β-amyloid protein CA1 神経細胞死

项目摘要

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.

本研究的最终目标是检查β-淀粉样蛋白和臀类肽-1（GLP-1）之间相互作用的细胞内机制（GLP-1）在脑功能障碍的进展中，并检查GLP-1在脑发育中的身体作用。 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机制，以及p38 MAP激酶的激活可能与P-淀粉样蛋白诱导的突触可塑性功能障碍以及与GLP-1的相互作用相互作用。Furthermore，我们发现胚胎中的组成型GLP-1在胚胎中的存在，而不是通过抑制了GLP的抑制作用，但在phippus pots propts stropts stropt propts stroption stroption in-P.培养的海马神经元具有GLP-1受体，而GLP-1受体的拮抗剂抑制了神经调节，对细胞活力没有任何影响。我们的结果表明，cAMP浓度和MAP激酶途径的激活涉及内源性GLP-1的作用。在培养的脑皮层神经元和培养的脊柱神经元中也观察到了相同的作用。这些结果表明，内源性GLP-1充当大鼠胚胎大脑中的神经营养因子，并且GLP-1可能通过促进神经元网络对受损大脑的治疗作用。