Xin Wang
Harvard Medical School, USA
Title: N-acetyl-serotonin and melatonin offer neuroprotection in experimental models of ischemic injury
Biography
Biography: Xin Wang
Abstract
The identifi cation of neuroprotective agents for stroke remains elusive. We therefore test whether melatonin receptor 1A agonists\\r\\nN-acetyl-serotonin (NAS) and melatonin are neuroprotective in experimental models of ischemic injury.\\r\\nWe demonstrate that NAS and melatonin inhibits cell death induced by oxygen-glucose deprivation or H2O2 in primary\\r\\ncerebrocortical neurons and primary hippocampal neurons in vitro, and/or organotypic hippocampal slice cultures ex vivo. We\\r\\nfurther found that NAS and melatonin reduce hypoxia/ischemia injury in the middle cerebral artery occlusion mouse model of\\r\\ncerebral ischemia in vivo. Our data show that NAS and melatonin are neuroprotective by inhibiting the mitochondrial cell death\\r\\npathway including the inhibition of the release of apoptogenic factors cytochrome c, Smac, and apoptosis-inducing factor from\\r\\nmitochondria to cytoplasm, and activation of caspase-3, -9. Furthermore, pro–IL-1 processing, and activation of caspase -1 are\\r\\nevaluated in melatonin-mediated neuroprotection. Moreover, we demonstrate that the neuroprotective eff ects of NAS may result\\r\\nfrom the infl uence of mitochondrial permeability transition pore opening, mitochondrial fragmentation, as well as the suppression\\r\\nof the autophagic cell death pathway under stress conditions by increasing LC3-II and Beclin-1 levels and decreasing p62 level.\\r\\nTaken together, we conclude that melatonin receptor 1A agonists NAS and melatonin have the potential as the novel therapies for\\r\\nischemic injury.