Melatonin attenuates cerebral hypoperfusion-induced hippocampal damage and memory deficits in rats by suppressing TRPM7 channels

Abstract

This study was conducted to examine if modulating transporters like transient receptor potential cation channels, subfamily M, member 7 (TRPM7) underlies the hippocampal neuroprotection afforded by melatonin (Mel) in rats exposed to cerebral hypoperfusion (CHP). Experimental groups included control, Mel-treated (1.87 g/kg), CHP, and CHP + Mel (1.87 g/kg)-treated rats. CHP was induced by the permanent bilateral occlusion of the common carotid arteries (2VO) method and treatments were conducted for 7 days, orally. Mel prevented the damage of the dental gyrus and memory loss in CHP rats and inhibited the hippocampal reactive oxygen species (ROS), lipid peroxidation levels of tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6), interleukine-1 beta (IL-1β), and prostaglandin E2 (PGE2). It also reduced the hippocampal transcription of the TRPM7 channels and lowered levels of calcium (Ca2+) and zinc (Zn2+). Mel Also enhanced the levels of total glutathione (GSH) and superoxide dismutase (SOD) in the hippocampus of the control and CHP-treated rats. In conclusion, downregulation of TRPM7 seems to be one mechanism underlying the neuroprotective effect of Mel against global ischemia and is triggered by its antioxidant potential.

Keywords

• Melatonin
• Ischemia
• Cerebral hypoperfusion
• TRPM7
• Calcium
• Oxidative stress