The Protective Effect of Melatonin against Monosodium Glutamate-induced Hippocampal Injury: Focused on Regulating the Nrf2/Heme Oxygenase 1 and nuclear factor-kappa β/Tumor Necrosis Factor-α/Caspase 3 and Brain Derived Neurotrophic Factor Signaling P

Background: Monosodium glutamate (MSG) is a fine white crystalline material. It is added to many numerous types of food as it improves the flavor of many processed products. However, a number of studies documented systemic detrimental effects. Aims: The current research investigated the histological and immunohistochemical changes that may develop in rat cornu ammonis (CA) 1, CA3 hippocampus, and dentate gyrus (DG) experimentally exposed to MSG and the possible neuroprotective role of melatonin. Materials and Methods: Thirty-two male albino rats were allocated randomly into four equal groups; the control group, melatonin-treated group, received IP injections of melatonin (6 mg/kg/day), MSG-treated group injected IP with MSG (4 mg/kg/day), and MSG + melatonin-treated group injected IP the aforementioned dose of MSG accompanied with melatonin for 14 days. The brains were carefully dissected and sectioned for the staining with hematoxylin and eosin, Cresyl violet, and immunohistochemical staining. Results: The data of the current research showed that IP administration of MSG decreased the number of pyramidal cell layers in CA1 and CA3 areas of the hippocampus due to neuronal cell death. In addition DG neurons revealed granular cells with shrunken cell bodies, deeply stained cytoplasm, and pyknotic nuclei with some areas of cellular loss. Conclusion: The current study’s findings demonstrate the neuroprotective benefits of melatonin, a naturally occurring antioxidant that restores normal redox activity and improves cells regeneration.