Protection of melatonin in experimental models of newborn hypoxic-ischemic brain injury through MT1 receptor

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

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere12443
JournalJournal of Pineal Research
Volume64
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Melatonin MT1 Receptor
Melatonin
Brain Injuries
Theoretical Models
Cell Death
Melatonin Receptors
Protective Agents
Neuroprotective Agents
Knockout Mice
Up-Regulation
Observation
Mortality
Brain

Keywords

  • hypoxic-ischemic brain injury
  • melatonin
  • MT1
  • newborn

ASJC Scopus subject areas

  • Endocrinology

Cite this

Protection of melatonin in experimental models of newborn hypoxic-ischemic brain injury through MT1 receptor. / Sinha, Bharati; Wu, Qiaofeng; Li, Wei; Tu, Yanyang; Sirianni, Ana C.; Chen, Yanchun; Jiang, Jiying; Zhang, Xinmu; Chen, Wu; Zhou, Shuanhu; Reiter, Russel J; Manning, Simon M.; Patel, Nirav J.; Aziz-Sultan, Ali M.; Inder, Terrie E.; Friedlander, Robert M.; Fu, Jianfang; Wang, Xin.

In: Journal of Pineal Research, Vol. 64, No. 1, e12443, 01.01.2018.

Research output: Contribution to journalArticle

Sinha, B, Wu, Q, Li, W, Tu, Y, Sirianni, AC, Chen, Y, Jiang, J, Zhang, X, Chen, W, Zhou, S, Reiter, RJ, Manning, SM, Patel, NJ, Aziz-Sultan, AM, Inder, TE, Friedlander, RM, Fu, J & Wang, X 2018, 'Protection of melatonin in experimental models of newborn hypoxic-ischemic brain injury through MT1 receptor', Journal of Pineal Research, vol. 64, no. 1, e12443. https://doi.org/10.1111/jpi.12443
Sinha, Bharati ; Wu, Qiaofeng ; Li, Wei ; Tu, Yanyang ; Sirianni, Ana C. ; Chen, Yanchun ; Jiang, Jiying ; Zhang, Xinmu ; Chen, Wu ; Zhou, Shuanhu ; Reiter, Russel J ; Manning, Simon M. ; Patel, Nirav J. ; Aziz-Sultan, Ali M. ; Inder, Terrie E. ; Friedlander, Robert M. ; Fu, Jianfang ; Wang, Xin. / Protection of melatonin in experimental models of newborn hypoxic-ischemic brain injury through MT1 receptor. In: Journal of Pineal Research. 2018 ; Vol. 64, No. 1.
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