Peptidic exenatide and herbal catalpol mediate neuroprotection via the hippocampal GLP-1 receptor/β-endorphin pathway.

摘要: Both peptidic agonist exenatide and herbal catalpol of the glucagon-like peptide-1 receptor (GLP-1R) are neuroprotective. We have previously shown that activation spinal GLP-1Rs expresses β-endorphin in microglia to produce antinociception. The aim this study was explore whether exert neuroprotection via hippocampal GLP-1R/β-endorphin pathway. rat middle cerebral artery occlusion model employed, GLP-1R immunofluorescence staining measurement were assayed hippocampus primary cultures microglia, neurons astrocytes. immunoreactivity on upregulated after ischemia reperfusion. Intracerebroventricular (i.c.v.) injection produced transient ischemia/reperfusion model, reflected by a marked reduction brain infarction size mild recovery neurobehavioral deficits. In addition, i.c.v. significantly stimulated expression cultured (but not or astrocytes). Furthermore, completely blocked orthosteric antagonist exendin (9-39), specific antiserum, selective opioid naloxone. Our results indicate, for first time, neuroprotective effects GLP-1R-specific, these mediated probably microglia. postulate contrast peripheral tissue, where pancreas islet β-cells causes secretion insulin perform glucoregulation, it leads microglial cells analgesia central nervous system.