PROTECTIVE EFFECT OF MELATONIN AGAINST HIPPOCAMPAL DNA-DAMAGE INDUCEDBY INTRAPERITONEAL ADMINISTRATION OF KAINATE TO RATS

The pineal hormone melatonin protects neurons in vitro from excitotoxi city mediated by kainate-sensitive glutamate receptors and from oxidat ive stress-induced DNA damage and apoptosis. Intraperitoneal injection on kainate into experimental animals triggers DNA damage in several b rain areas, including the hippocampus. It is not clear whether melaton in is neuroprotective in vivo. In this study, we tested the in vivo ef ficacy of melatonin in preventing kainate-induced DNA damage in the hi ppocampus of adult male Wistar rats. Melatonin and kainate were inject ed i.p. Rats were killed six to 72 h later and their hippocampi were e xamined for evidence of DNA damage (in situ dUTP-end-labeling, i.e. TU NEL staining) and for cell viability (Nissl staining). Quantitative as say was performed using computerized image analysis. At 48 and 72 h af ter kainate we found TUNEL-positive cells in the CAI region of the hip pocampus; in the adjacent sections that were Nissl-stained, we found e vidence of cell loss. Both the number of TUNEL-positive cells and the loss of Nissl staining were reduced by i.p. administration of melatoni n (4 x 2.5 mg/kg; i.e. 20 min before kainate, immediately after, and 1 and 2 h after the kainate). Our results suggest that melatonin might reduce the extent of cell damage associated with pathologies such as e pilepsy that involve the activation of kainate-sensitive glutamate rec eptors. Copyright (C) 1996 IBRO.