Protection of melatonin in experimental models of newborn hypoxic-ischemic brain injury through MT1 receptor.
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| Abstract |
The function of melatonin as a protective agent against newborn hypoxic-ischemic (H-I) brain injury is not yet well studied, and the mechanisms by which melatonin causes neuroprotection in neurological diseases are still evolving. This study was designed to investigate whether expression of MT1 receptors is reduced in newborn H-I brain injury and whether the protective action of melatonin is by alterations of the MT1 receptors. We demonstrated that there was significant reduction in MT1 receptors in ischemic brain of mouse pups in vivo following H-I brain injury and that melatonin offers neuroprotection through upregulation of MT1 receptors. The role of MT1 receptors was further supported by observation of increased mortality in MT1 knockout mice following H-I brain injury and the reversal of the inhibitory role of melatonin on mitochondrial cell death pathways by the melatonin receptor antagonist, luzindole. These data demonstrate that melatonin mediates its neuroprotective effect in mouse models of newborn H-I brain injury, at least in part, by the restoration of MT1 receptors, the inhibition of mitochondrial cell death pathways and the suppression of astrocytic and microglial activation.
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| Authors | Bharati Sinha, Qiaofeng Wu, Wei Li, Yanyang Tu, Ana C Sirianni, Yanchun Chen, Jiying Jiang, Xinmu Zhang, Wu Chen, Shuanhu Zhou, Russel J Reiter, Simon M Manning, Nirav J Patel, Ali M Aziz-Sultan, Terrie E Inder, Robert M Friedlander, Jianfang Fu, Xin Wang |
| Journal | Journal of pineal research (J Pineal Res) Vol. 64 Issue 1 (Jan 2018) ISSN: 1600-079X [Electronic] England |
| PMID | 28796402 (Publication Type: Journal Article) |
| Copyright | © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. |
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