Impaired Mechanism Of Kainate On Rats Neuron And Protective Effects Of Melatonin Againt The Damage By Kainate

ABSTRACTOBJECTIVES:To investigate impaired effect of excitatory amino acids(EAAs) caused by intrperitioneal administration of kainate(KA) to rats neuron and protective effects of melatonin (MT) against the damage by KA. MEHTODS: (l).After tested by Y-type maze, the rats with normal study ablity were randomly divided into two groups including the experimental group with intrperitioneal administration of kainate(KA) and the control group with intrperitioneal administration of same volume vehicle, however, the rats with dysfunction of learning were eliminated. AS soon as the rats both of experiment and control were fed for 7 days, Y-type maze test was performed once more, and the hippocampal simples of brain were histochemical studied by acetycholinesterase (AChE) and by SABC method for neuronal substance P(SP). (2). The rats were divided into tow groups randomly after tested by Y-type maze and those with dysfunction of learning were eliminated. The experimental group was performed by intraperitioneal administration of kainate(KA), the control was treated by same volume vehicle in same way. after fed for ten days ,the brain hippocampal tissues of rats were stained by Nissl and AChE method respectively, active microglia was observed by SABC immunohistochemical assay of CD4,astrocyte was studied by SP method for glial fibrillary acidic protein(GFAP). (3).The rats with normal study ablity were randomly divided into two groups including the experimented group with administration of kainate(KA) by intraperiton and the contral group with administration of same volume vehicle in same way,after for fed three days ,The neuronic apoptosis in the hippocampus were examined with terminal deoxynucleotidyl-transferase mediated d-UTP-biotin nick end labeling (TUNEL), related gene Bax and Bcl-2 expression were marked by SABC method.(4).The rats were divided into three groups randomly. Experimented group was treated by kainate(KA),the treatment group was performed by kainate(KA) and melatonin (MT) and the blankcontral was teated by the vehicle.At the 3th, neuronic apoptosis in the hippocampus were examined with terminal deoxynucleotidyl-transferase mediated d-UTP-biotin nick end labeling (TUNEL), neuronal loss was examined by Niss staining. RESULTS: (1).The rats of administration of kainate(KA), showed decreased learning and memory ability, the AChE-positive fibers density in the hippocampus was more significant decreased than those of the control rats in the hippocampus. The Substance-P contents of in the hippocampus of experimental rats was significantly increased than that of control rats. (2). The experiment showed that the AchE-posistive fibers density of in the hippocampus of experimental rats was significantly decreased than that of control rats. The number of CD4-positi~e and GFAP-positive cell in the hippocampus of experimented group were significantly increased than that of contral ones. (3).Kainate can induce neuronic apoptosis,up-regulation of bax and dwon-regulation of bcl-2 in the hippocampus of rats by intraperitoneal administration. (4).Melatonin can reduce neuronic apoptosis in the hippocampus indused by intrperitioneal administration of kainate(KA) to rats. CONCLUSIONS: (1) Intrperitioneal administration of kainate(KA) to rats resulted in disorder of learning and memory and the reason may be correlated with reduction of cholinergic fibers density in the hippocampus (2). Increasing of substance-P content and elevated activity of microglia and astrocyte in the hippocampus of rats might be involved in the pathophysiologic course lose of neuron of by kainite(KA). (3).Protective effect of melatonin against hippocampal neuronic apoptosis induced by intrperitioneal administration of kainate(KA) to rats, however, the neuronic apoptosis can not be inhibited thoroughly.