Melatonin protects MCAO-induced neuronal loss via NR2A mediated prosurvival pathways

Author First name, Last name, Institution

Fawad Ali Shah, Peking University
Gongping Liu, Huazhong University of Science and Technology
Lina T. Al Kury, Zayed UniversityFollow
Alam Zeb, Riphah International University
Muzaffar Abbas, Capital University of Science & Technology
Tao Li, Xi'an Jiaotong University
Xifei Yang, Centre for Addiction and Mental Health
Fang Liu, University of Toronto
Yuhua Jiang, Second Hospital of Shandong University
Shupeng Li, Peking University

Document Type

Article

Source of Publication

Frontiers in Pharmacology

Publication Date

1-1-2019

Abstract

© 2019 Shah, Liu, Al Kury, Zeb, Abbas, Li, Yang, Liu, Jiang and Li. Stroke is the significant cause of human mortality and sufferings depending upon race and demographic location. Melatonin is a potent antioxidant that exerts protective effects in differential experimental stroke models. Several mechanisms have been previously suggested for the neuroprotective effects of melatonin in ischemic brain injury. The aim of this study is to investigate whether melatonin treatment affects the glutamate N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor signaling in cerebral cortex and striatum 24 h after permanent middle cerebral artery occlusion (MCAO). Melatonin (5 mg/kg) attenuated ischemia-induced down regulation of NMDA receptor 2 (NR2a), postsynaptic density-95 (PSD95) and increases NR2a/PSD95 complex association, which further activates the pro-survival PI3K/Akt/GSK3β pathway with mitigated collapsin response mediator protein 2 (CRMP2) phosphorylation. Furthermore, melatonin increases the expression of γ-enolase, a neurotrophic factor in ischemic cortex and striatum, and preserve the expression of presynaptic (synaptophysin and SNAP25) and postsynaptic (p-GluR1845) protein. Our study demonstrated a novel neuroprotective mechanism for melatonin in ischemic brain injury which could be a promising neuroprotective agent for the treatment of ischemic stroke.

DOI Link

10.3389/fphar.2019.00297

ISSN

1663-9812

Publisher

Frontiers Media S.A.

Volume

10

Issue

MAR

First Page

297

Disciplines

Medicine and Health Sciences

Keywords

AMPA receptor, Ischemic stroke, Melatonin, NMDA receptor, PI3K/AKT/GSK3 pathway

Scopus ID

85066449579

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Shah, Fawad Ali; Liu, Gongping; Al Kury, Lina T.; Zeb, Alam; Abbas, Muzaffar; Li, Tao; Yang, Xifei; Liu, Fang; Jiang, Yuhua; and Li, Shupeng, "Melatonin protects MCAO-induced neuronal loss via NR2A mediated prosurvival pathways" (2019). All Works. 2362.
https://zuscholars.zu.ac.ae/works/2362

Indexed in Scopus

yes

Open Access

yes

Open Access Type

Gold: This publication is openly available in an open access journal/series