| Antagonistic Effect of Melatonin on Experimental Alzheimer's disease and Its Mechanism of ActionAlzheimer's disease (AD) is a neurodegenerative disease that causes progressive cognitive and behavior deterioration in the elderly, and it is the most common cause of senile dementia. The number of people with AD increases with aging. Currently, there is no cure for this disease because the etiopathology of AD remains unknown. Melatonin has been known as a neuroendohormone synthesized and secreted primarily by the pineal gland. Among known antioxidant, Melatonin is the most effective scavenger of free radicals in vivo. Melatonin possesses some important physiological and pharmacological effects, for example, anti-aging, hypnotizing, analgesic activity and neuroprotective action, etc.Lately, the effect on AD has been noted. It was suggested, by clinical and experimental data, that Melatonin could be useful to treat AD. For this study, two AD models were established first, included mouse model inducing by aluminum chloride and rat model induced by okadaic acid (OA). Meanwhile, the AD model was administered with melatonin. Then the learning and memory ability of models were examined by step-through test and performance in Morris water maze, and the pathological changes in AD model brain were observed with Bielschowsky stain. This study will be useful to clarify the effect of melatonin on AD. Based on these study, the activities of superoxide dismutases (SOD), glutathione peroxidases (GSH-Px) and the content of malondialdehyde (MDA) in mice model brain were detected, and tau protein in rat model brain were half-quantitatively determined by Western Blot. Through the study above, the mechanism of action of melatonin on AD was analyzed.1. AD model1.1 Mouse AD model induced by aluminumBy step-through test and performance in Morris water maze, the effect of aluminum chloride on the learning and memory ability in mice were observed after mice were treated with intracerebroventricular injection of aluminum chloride and the pathological changes in mouse were observed by Bielschowsky stain. The result of step-through test showed that the latency of model mice was shorter than that in control (P<0.05) and the number of error in model mice was much more than that in control (P<0.01). It suggested that the passive avoidance and memory ability hi mice were damaged by aluminum chloride. From the result of performance in Morris water maze, it was seen that the latency in model mouse was longer than that in control (PO.01) by place navigation test, and the lingering time of model mouse in platform area was shorter than that of control (PO.01) by spatial probe test. This study shows that the spatial learning and memory ability in model mice has been damaged. In the hippocampal coronal section of models, fused, disordered and thickened neurofibrils and still a few neurofibrillary tangles were found by Bielschowsky stain. From the above, it were showed that the passive avoidance and memory ability, and spatial learning and memory ability in mice can be damaged by intracerebroventricular injection of aluminum chloride, and the appearance of learning and memory impairment and characteristic pathological changes such as SP and NFT in AD strongly suggest that this model may be a useful model for AD study.1.2 Rat AD model induced by okadaic acidEffect of okadaic acid on learning and memory ability in rat was measured by Morris water maze and the pathological changes in mouse were observed by Bielschowsky stain. The result of place navigation test showed that the latency hi model rat was longer than that in control (PO.OI). From spatial probe test, it was seen that the lingering tune of model rat hi platform area was shorter than that of control (P<0.01). In hippocampal coronal section of AD models, fused disordered and thickened neurofibrils, still a few neurofibrillary tangles and senile plaques were observed by Bielschowsky stain. From the above, it was showed that the spatial learning and memory ability in rat can... |
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