The Change Of MGluR1α And GLT In Brain Of Aging Mouses D-glactose Treated

The D-galactose is one of physiological nutrient, which can be metabolize into glucose and participate in organism metabolism. However the excessive D-galactose will cause the metabolic disorder. D-galactose treatment can cause manifests similar whit natulal aging animal, for example, immuno-compromice, descent of cells'reproductive capacity, recessive change of cells, dysgnosia and so on. At present, this aging model has used in research regarding ageing mechanism and disease peculiar to old age because of its finer simulation.Glutamate (Glu) is one of amino acid participated in organism metabolism. And at the same time, it is the overriding excitatoty neurotransmitter in brain, main in cerebral cortex, hippocampus, cerebellum and corpus striatum. As one of group I metabotropic gluatamate receptor (mGluR), mGluR1αis located at postsynaptic membrane, main in cerebral cortex, hippocampus. The activation of mGluRlaparticipate excitatory synaptic transmission, regulate normal physiologic function in CNS, and reinforce excitatory toxicity mediated by ionotropic gluatamate receptor(iGluR). As one of five glutamate ransporters (EAAT), GLT (EAAT2) is a kind of carrier protein. GLT located in cell membrane of gliacyte and neuronic, the expression of GLT is mainly in prosencephalon, cerebral cortex, hippocampus and striatum. The main effect that reuptake Glu is completed by GLT-1 and GLAST (EAAT1)Aging models take important part in aging research. Studes show that D-galactose treatment can cause manifests similar whit natulal aging animal, but the mechanism is indefinite now. Many scholars deem that it is caused by galactitol poisoning; and many other think that it is caused by overloaded free radicals.The dopamine (DA) in SN-striatum system is important transmitter in extrapyramidal system, therefore it concerned with body movement. The motor function is reinforced when DAenergic neurons is reinforced, and weakened when it is weakened. The long-term potentiation (LTP) in hippocampus is basic on trisynaptic circuit, and the neuromechanism of memory creation is basic on LTP. Therefore, the change of Glu system in SN-striatum and hippocampus can cause neurons damnification, and result in behavioral change and cognition disorders.Objective:The HE, Nissl and immuocytochemistry were used in this study to observe the changes of the neurons number and the glutamate system in D-gal mouses, to discuss the influence of D-galactose treatment on the expression of mGluRlaand GLT of mouses, to probe into the imaginabale mechanism of action of inducing aging.Methods:Mouses used for experiment were randomly divided into experimental and control groups. Animals in the experimental group were given a subcutaneous injection of 60mg/Kg/d D-galactose; and those in the control group were given an injection of physiological saline alone. HE, Nissl was used to analyze the alteration of neuron numbers, and immuocytochemistry was used to analyze the alteration of the expression of mGluR1αand GLT in mouses brain.Results:1. cell counting:Long-term D-galactose treatment decreased the neuron numbers in substantia nigra. The neuron numbers are 27.78±4.77 (D-gal) and 157.23±5.57 (Con) in substantia nigra, it is significently lower than that of control(P<0.01).2. The experimental results of immunohistochemical staining:①The results of mGluRl immunohistochemical staining:Long-term D-galactose treatment increased the expression of mGluRla in hippocampus, substantia nigra and striatum of mouse. The gray scale mean value are 151.50±8.26 (D-gal) and 157.23±5.57 (Con) in substantia nigra,148.51±9.80 (D-gal) and 154.35±7.70 (Con) in striatum,155.04±8.05 (D-gal) and 158.89±7.15 (Con) in stratum radiatum,154.29±6.41 (D-gal) and 158.89±8.31 (Con) in stratum oriens. Indicating that the gray scale mean value of mGluRla in stratum radiatum of hippocampus, substantia nigra and striatum of the experimental are significently lower than that of control(P<0.01),and that in stratum oriens of hippocampus is lower than that of control(P<0.05).②The results of GLT immunohistochemical staining:Long-term D-galactose treatment reduced the expression of GLT in hippocampus and substantia nigra of mouse. The gray scale mean value are 151.06±5.94 (D-gal) and 141.03±8.00 (Con) in substantia nigra,157.46±6.03 (D-gal) and 157.37±6.14 (Con) in striatum, 153.89±7.50 (D-gal) and 151.00±9.17 (Con) in stratum pyrami. Indicating that the gray scale mean value of GLT in substantia nigra of the experimental are significently higher than that of control(P<0.01), in stratum pyrami of the experimental are higher than that of control(P<0.05), and no significant change in corpus striatum (P>0.05)Conclusion:1. Long-term D-galactose treatment decreased the neuron numbers in substantia nigra; 2. Long-term D-galactose treatment increased the mGluR1αcontent in hippocampus, substantia nigra and corpus striatum of mouses; 3. Long-term D-galactose treatment reduced the GLT content in hippocampus and substantia nigra of mousse; 4. The altered gluatamate receptor and glutamate ransporter in long-term D-galactose treated mousse may influence the neuron numbers, which may be related to the aging.