Melatonin improves hypoxic-ischemic brain damage through the Akt/Nrf2/Gpx4 signaling pathway

  • Brain Res Bull. 2020 Oct;163:40-48. doi: 10.1016/j.brainresbull.2020.07.011.
Zhixian Gou  1 ,  Xiaojuan Su  2 ,  Xing Hu  1 ,  Yue Zhou  1 ,  Lin Huang  1 ,  Yang Fan  1 ,  Jing Li  3 ,  Liqun Lu  4
Affiliations
  • 1. Department of Pediatrics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, China.
  • 2. Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children(Ministry of Education), West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
  • 3. Clinical Laboratory, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, China.
  • 4. Department of Pediatrics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, China. Electronic address: [email protected].
PMID: 32679060 DOI: 10.1016/j.brainresbull.2020.07.011
Abstract

Melatonin (Mel) has neuroprotective effects; however, its roles in hypoxic-ischemic brain damage (HIBD) and the underlying mechanisms remain unknown. We aimed to explore its roles and mechanisms in a HIBD rat model. We found that exogenous Mel treatment ameliorated HIBD-induced pathological changes, inhibited neuronal Ferroptosis, and promoted hippocampal neuronal survival. Moreover, Mel improved the learning and memory abilities of the HIBD rats. Further, we found that Glutathione Peroxidase 4 (Gpx4) inhibition with RSL3, Akt inhibition with LY29400, and nuclear factor erythroid-2-related factor 2 (Nrf2) inhibition with ML385 abolished the Mel protective effects in HIBD. Our findings indicate that exogenous Mel treatment has a protective effect on HIBD via the Akt/Nrf2/Gpx4 pathway.

Keywords
Akt/ Nrf2/Gpx4; Ferroptosis; Hypoxic-ischemic brain damage; Melatonin; Neuron.
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