Establishment Of Aging Model Induced By D-galactose And Study On Impairment Of Cognitive Function In Mice

In recent years, the problem about population aging has become more and more serious all over the world. Various diseases followed with increment of the proportion of aging population. It seems to be very urgent to perform research on mechanisms of aging in order to prolonging life. Establishing aging animal model is essential for studying aging mechanisms and for screening of effective agents that can delay process of aging. In present investigations on aging delay, most of the internal researchers use subacute aging model induced by D-galactose injection. The subacute aging model was proposed firstly by Prof. Xu. He found the model mice had some similar physiological and biological changes with natural aging mice, which led to an accelerated aging.In present research, we detect some crucial physiological indexes and examine behavior performance firstly, to choose the best D-galactose dosage for establishing the aging model. Then, under this dosage, experiments were performed to investigate the influence of long term D-galactose exposure on cognitive function in mice. We also check the effects on physiological indexes in hippocampus and prefrontal cortex of model mice. The present thesis has 4 parts as follows:1. The paper gives a comprehensive introduction of senescence, including history of research about aging , main theories and hypotheses, methods;2. Describe the subacute aging model's mechanism, and make a review of recent research about aging model induced by D-galactose;3. The method to establish subacute aging model is introduced, and try to find the best dose range of D-galactose;4. Investigate the impairment of cognitive function of aging model induced by D-galactose, and discuss possible reasons for such cognitive impairment.The results showed that, in the range of 120-150mg/kg/d, D-galactose caused decline of antioxidant enzyme's activity, meanwhile it also did damage to cognitive function. However, the effect of 75mg/kg/d D-galactose was not significantly. Moreover, 1000 mg/kg/d D-galactose caused similar changes as mentioned above, although it led to decline of immune function and increment of death rate, decrease of locomotor activity. These changes were disadvantageous for behavior test and performance invaluation. So 120-150mg/kg/d were selected as the proper range of D-galactose dosage.The present research also found the spatial, but not non-spatial, cognitive function of mice was seriously damaged after long-term D-galactose injection. Antioxidant enzyme activity decreased in both hippocampus and prefrontal cortex of model mice, although the changes were more significant in hippocampus. Moreover, expression of apoptosis associated protein caspase-3 in hippocampus and prefrontal cortex increased. Because hippocampus and prefrontal cortex played important roles in cognition function, spatial cognitive impairment maybe related with the changes of antioxidant enzyme activity and neuronal apoptosis in relative brain regions.