The Effects Of Rehabilitative Training On The Behaviors Of Parkinson's Disease Mouse And Underlying Mechanism

Background and Objective:Parkinson's disease(PD) is a chronic progressive neurodegenerative disease among middle age and old-age persons.Its clinical characteristics include tremor, rigidity, bradykinesia and postural instability.The principal neuropathological characteristic of PD is shortage of dopamine(DA) neurons in the substantia nigra pars compacta and degeneration of the substantia nigrostriatal pathway. The number of PD is increasing year by year as people live longer than before.Therefore, the study of PD has become more and more extensive.Now the cause of PD is unknown, PD is caused by the severe shortage of dopaminergic neurons in the substantia nigra pars compacta, the depletion of neurotransmitter dopamine in the stratum and Sustantia nigra (SN) and the decrease of tyrosine hydroxylase activity. DA is one of the most important molecules in accommodating body movement,the depletion of DA is the direct reason for abnormal motor behavior in PD. TH(tyrosine hydroxylase,TH) catalyzes the hydroxylation of 1-tyrosine to 1-dihydroxyphenylalanine, the rate-liniting step in the biosynthesis of DA. Thus increasing the number of TH and improving the activity of TH can accelerate the growth of DA, improve the function of the dopaminergic nerve system and promote the ability of movement in PD. Glial fibrillary acidic protein(GFAP) has abundant expression in active Astrocyte.All kinds of brain damages could excite mature Astrocyte to synthesize GFAP.The process of neuroglia activing was a particular reaction to any serious damage of brain and characteristic by proliferation and swelled cell, which can exist continuously. The proliferation extent of Astrocyte and the damaging extent of brain can be evaluated by expression of GFAP. The content of GFAP will increase probably in the brain of PD patient and decrease after therapy. Now the major therapy is the symptomatic treatment, which can alleviate many clinical symptoms, but induce many side effects such as decreasing curative effects,symptom repeating, handicapping motor and spirit if it takes a long period.There is no treatment that can prevent or arrest the disease procession, so many doctors and scicentits are looking for neuroprotective drug to prolong,prevent and adverse neuron changing in order to protect neuron. Rehabilitative training gives a hope in curing PD. In this experiment,we studied the effects of rehabilitative training on behaviors, the content of dopamine and its metabolites,3,4-dihydroxyphenylacetic acid(DOPAC) and homovanillic acid(HVA), tyrosine hydroxylase and glial fibrillary acidic protein in the Parkinson's disease mouse brain and discussed the possible mechanism of the effect of rehabilitative training on PD's mouse.Methods:1.Sample preparation:96 male C57BL/6J mice were divided normal group,fake-operative group,model group and rehabilitative group randomly.The normal mice didn't give any treatment,the fake-operative group were injected saline liquid into the belly and didn't give any treatment. The mice of model group and rehabilitative group were injected MPTP into the belly to establish PD model, then the model group didn't give any treatment, the rehabilitative group were given rehabilitative training, one per day, lasting 4 weeks.2. Observed the mice behaviors of each group respectively after 0 week,l week,2 week and 4 week training.At the same time, made the samples of brain tissues in different periods and different groups, detected the content of DA and its metabolites, tested the expressive changes of GFAP and TH by the method of immuno-histochemical staining, collected the useful data and made an analysis.Results:1.The function of mice limbs decreased significantly after 0 week's rehabilitative training in model group and rehabilitative group,but after 2 weeks' rehabilitative training,the function of rehabilitative mice limbs improved significantly,there was a significant difference between the two groups.The function of model mice limbs didn't improve after 4 weeks'rehabilitative training, there was a significant difference when comparing with that of rehabilitative group mice. In the model group, there wasn't a significant difference between after 2 weeks and after 4 weeks.2. The content of nigrostriatal DA and its metabolites decreased in the model group and the rehabilitative group before rehabilitation, which had a significant difference when comparing with that of the normal group and the fake-operative group.There was a significant improvement in the rehabilitative group but not in the model group after 2 weeks'training.There wasn't a significant improvement in the model group after 4 weeks'training while the content of nigrostriatal DA and its metabolites in the rehabilitative group improved significantly. In the model group, there wasn't a significant difference between after 2 weeks and after 4 weeks.3. The TH positive cell number decreased in the model group and the rehabilitative group before rehabilitation, there was a significant difference comparing with the mice of normal group and fake-operative group. There was a significant improving in the rehabilitative group but not in the model group after 2 weeks' training, There wasn't a significant improvement in the model group after 4 weeks' training while the number of TH in rehabilitative group improved significantly. In the model group, there wasn't a significant difference between after 2 weeks and ater 4 weeks.4. There were a few GFAP positive cell in the model group and the fake-operative group,the numbers of GFAP increased greatly in the model group and the rehabilitative group, which had a significant difference comparing with the normal group, there is no significant difference between the rehabilitative group and the model group. After 4 weeks'training, the GFAP positive cell numbers of the rehabilitative group decreased greatly, There was a significant difference between the rehabilitative group and the model group. In the model group, there wasn't a significant difference between after 2 week and after 4 week.Conclusions:1. Mice had the motor characteristics of PD after injecting MPTP into the belly. Rehabilitative training can improve the motor ability of the PD mice.2. Rehabilitative training improving the motorial ability of the PD mice is relative to the increasing of the the content of DA.3. The TH number of the PD mice can be increased by rehabilitative training, so did the content of DA and its metabolites, which probably was relative to the recovery of the nerves and the improving of the action of the mice.4. Rehabilitative training promoting the recovery of motorial function of PD mice is related to its alleviating the active reaction of astrocyte.