Pediatrics & Therapeutics
Open Access
ISSN: 2161-0665
+44 1478 350008
ISSN: 2161-0665
+44 1478 350008
Xin Wang
Brigham and Women��?s Hospital, USA
Scientific Tracks Abstracts: Pediat Therapeut
We and other researchers have reported that melatonin plays neuroprotective role in a variety of neurological conditions including acute cerebral ischemia and chronic Huntington��?s disease and Amyotrophic lateral sclerosis. However its role as a protective agent against newborn hypoxic-ischemic (H-I) brain injury is not yet well studied, while the mechanisms by which melatonin causes neuroprotection in neurological diseases is still evolving. The present study demonstrated that there was significant reduction in MT1 receptors in ischemic brain in mouse pups in vivo with H-I brain injury and in primary cortical neurons and primary astrocytes in vitro as the result of environmental stress and melatonin offers protection through upregulation of MT1 receptors and inhibition of mitochondrial cell death pathways. The direct role of MT1 receptors was further supported by observation of increased mortality in MT1 knockout mice and the protective effects in neuronal cell death and the inhibitory role of mitochondrial cell death pathways including mitochondrial potential gradient dissipation, mitochondrial permeability transition pore opening, mitochondrial fragmentation, and inhibition of the subsequent cytochrome c/Smac/AIF releases and caspase-3 activation by melatonin were reversed by melatonin receptor antagonist luzindole. Moreover, we found that the serum levels of melatonin were reduced in newborn pups with H-I injury. Taken together, these data demonstrate that melatonin mediates its neuroprotective effect in models of newborn H-I brain injury, at least in part, by the restoration of MT1 receptors and the inhibition of mitochondrial cell death pathways and suggest that serum melatonin level may serve as a potential biochemical biomarker for this devastating newborn condition.
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.
Email: xwang@rics.bwh.harvard.edu