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

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 (Ca(2+)) and zinc (Zn(2+)). 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.