Peptidic exenatide and herbal catalpol mediate neuroprotection via the hippocampal GLP-1 receptor/β-endorphin pathway
Peptidic exenatide and herbal catalpol mediate neuroprotection via the hippocampal GLP-1 receptor/β-endorphin pathway
复制标题
肽艾塞那肽和草药梓醇通过海马 GLP-1 受体/β-内啡肽途径介导神经保护
DOI：
10.1016/j.phrs.2015.10.008
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发表时间：
2015-12-01
影响因子：
9.3
通讯作者：
Wang, Yong-Xiang
中科院分区：
文献类型：
--
作者：
Jia, Yu;Gong, Nian;Wang, Yong-Xiang
Both peptidic agonist exenatide and herbal agonist catalpol of the glucagon-like peptide-1 receptor (GLP-1R) are neuroprotective. We have previously shown that activation of spinal GLP-1Rs expresses beta-endorphin in microglia to produce antinociception. The aim of this study was to explore whether exenatide and catalpol exert neuroprotection via activation of the hippocampal GLP-1R/beta-endorphin pathway. The rat middle cerebral artery occlusion model was employed, and the GLP-1R immunofluorescence staining and beta-endorphin measurement were assayed in the hippocampus and primary cultures of microglia, neurons and astrocytes. The immunoreactivity of GLP-1Rs on microglia in the hippocampus was upregulated after ischemia reperfusion. Intracerebroventricular (i.c.v.) injection of exenatide and catalpol produced neuroprotection in the rat transient ischemia/reperfusion model, reflected by a marked reduction in brain infarction size and a mild recovery in neurobehavioral deficits. In addition, i.c.v. injection of exenatide and catalpol significantly stimulated 3-endorphin expression in the hippocampus and cultured primary microglia (but not primary neurons or astrocytes). Furthermore, exenatide and catalpol neuroprotection was completely blocked by i.c.v. injection of the GLP-1R orthosteric antagonist exendin (9-39), specific beta-endorphin antiserum, and selective opioid receptor antagonist naloxone. Our results indicate, for the first time, that the neuroprotective effects of catalpol and exenatide are GLP-1R-specific, and that these effects are mediated by beta-endorphin expression probably in hippocampal microglia. We postulate that in contrast to the peripheral tissue, where the activation of GLP-1Rs in pancreas islet beta-cells causes secretion of insulin to perform glucoregulation, it leads to beta-endorphin expression in microglial cells to produce neuroprotection and analgesia in the central nervous system. (C) 2015 Elsevier Ltd. All rights reserved.
