Brain Disorders & Therapy

Identification of melatonin receptor 1A agonists as neuroprotective agents in experimental models of ischemic injury

Global Summit on Stroke

August 03-05, 2015 Birmingham, UK

Xin Wang

Scientific Tracks Abstracts: Brain Disord Ther

Abstract:

The identification of neuroprotective agents for stroke remains elusive. We therefore test whether melatonin receptor 1A
agonists melatonin, N-acetyl-serotonin (NAS) and ramelteon are neuroprotective in experimental models of ischemic
injury. We demonstrate that melatonin or NAS or ramelteon inhibits cell death induced by oxygen-glucose deprivation or H2O2
in primary cerebrocortical neurons and primary hippocampal neurons in vitro and organotypic hippocampal slice cultures ex
vivo. We further found that melatonin and NAS reduce hypoxia/ischemia injury in the middle cerebral artery occlusion mouse
model of cerebral ischemia in vivo. Our data show that melatonin and NAS are neuroprotective by inhibiting the mitochondrial
cell death pathway including the inhibition of the release of apoptogenic factors cytochrome C, Smac, and apoptosis-inducing
factor from mitochondria to cytoplasm, and activation of caspase-3, -9. Furthermore, pro–IL-1 processing, and activation of
caspase-1 are evaluated in melatonin-mediated neuroprotection. Moreover, we demonstrate that the neuroprotective effects
of NAS may result from the influence of mitochondrial permeability transition pore opening, mitochondrial fragmentation as
well as the suppression of the autophagic cell death pathway under stress conditions by increasing LC3-II and Beclin-1 levels
and decreasing p62 level. Taken together, we conclude that melatonin receptor 1A agonist’s melatonin, NAS and ramelteon
have the potential as the novel therapies for ischemic injury.

Biography :

Xin Wang is the Director of Neuroapoptosis Drug Discovery Laboratory, Department of Neurosurgery, Brigham and Women’s Hospital/Harvard Medical School. She
received her PhD from Hebrew University of Jerusalem. She did her Postdoctoral training at University of Michigan and Harvard Medical School. She has published
about 70 peer-reviewed articles and has served as the Guest Editor, Handling Editor, and Editorial Board Member for a number of peer-reviewed journals, as well
as the scientist reviewer for institutes or foundations including NIH, DOD, BSF, and others, and invited reviewer for 30 peer-reviewed journals.