Melatonin reduces the expression of excitotoxicity-triggered markers of apoptosis

In rats, intraperitoneal administration of the glutamate receptor agonist kainate triggered the expression of apoptotic markers p53 and DNA fragmentation in cells of the CA3 region of the hippocampus. Twenty-four hours after kainate administration, we observed a loss of Nissl staining in the CA3 and an increased number of GFAP-positive cells in the stratum radiatum of the CA1. Reduced expression of kainate-triggered apoptotic markers and a significant prevention of cell loss (Nissl staining) were obtained by either the intraperitoneal administration of melatonin, or when kainate was injected in the presence of elevated levels of endogenous melatonin, i.e., during the night. Further experiments are needed to elucidate the mechanism behind the prevention of excitotoxic neuronal death provided by melatonin. One possible mechanism is the antioxidative action of melatonin. Our results suggest that melatonin and/or melatonin derivatives may be considered putative neuroprotective molecules useful for the treatment of brain pathologies that involve excitotoxicity.