2. Academic Validation
  3. Melatonin improves hypoxic-ischemic brain damage through the Akt/Nrf2/Gpx4 signaling pathway

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

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: luliqun7@sina.com.
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.

Figures
Products