Xin Wang
Harvard Medical School, USA
Title: Melatonin offers neuroprotection in models of newborn hypoxic-ischemic brain injury through the restoration of MT1 receptors
Biography
Biography: Xin Wang
Abstract
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. 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.
