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The Effects of Rehabilitative Training on the Behaviors of Parkinson’s Disease Mouse and Underlying Mechanism

Author: LeLin
Tutor: ZhangBoAi
School: Zhengzhou University
Course: Neurology
Keywords: Parkinson's disease Rehabilitation Dopamine Tyrosine hydroxylase Glial fibrillary acidic protein
CLC: R742.5
Type: Master's thesis
Year: 2010
Downloads: 23
Quote: 0
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Abstract

Background and Purpose: Parkinson's disease (Parkinson's Disease, PD) is a progressive neurodegenerative disease common in the elderly, chronic, and its main clinical manifestations of resting tremor, muscle rigidity, movement disorders and balance disorders, and its main pathological features of the substantia nigra pars compacta dopaminergic neurons lack substantia nigra - degeneration of striatal pathway. To speed up the process of socio-demographic aging, disease prevalence increases every year, therefore, the study of the disease has caused widespread concern. Parkinson's disease pathogenesis is still remains unclear, studies have shown that PD patients substantia nigra pars compacta dopamine (dopamine, DA) neurons serious lack substantia nigra and striatal DA reduce tyrosine hydroxylase (tyrosine hydroxylase TH) activity decreased. DA is an important molecule regulating the function of human motion, DA level of reduction is the main reason to cause PD patients with movement disorders. TH is the rate-limiting enzyme of DA synthesis, thus increasing the number of TH TH activity promotes dopaminergic nerve growth, protection of dopaminergic nerve function, improve the exercise capacity of patients with PD. Abundant glial fibrillary acidic protein (glial fibrillary acidic protein, GFAP) in astrocytes (Astrocyte, Ast), relatively more GFAP expression in reactive astrocytes. All kinds of brain damage can be increased to stimulate astrocytes synthesis GFAP, this active glial process is a peculiar reaction of astrocytes on brain injury, astrocytes proliferation, cell body and excessive enlargement of the nucleus, and this reaction is sustainable, GFAP as an important sign of the degree of proliferation of astrocytes and the extent of brain tissue damage can be assessed GFAP expression studies have shown that PD patients with brain GFAP were significantly increased, decreased after treatment, the clinical symptoms were relieved. The treatment of Parkinson's disease is still the main drug treatment, can reduce the clinical symptoms in most patients, but long-term use will appear more side effects, such as to reduce the efficacy of fluctuations in symptoms as well as exercise and mental disorders, etc., and can not be prevent or delay the progressive loss of dopaminergic neurons. Therefore, people have been looking for to be able to slow down, stop or even reverse the neurodegenerative drugs protect neurons from loss. Certainly played the role of rehabilitation in the treatment of patients with brain injury, new inspiration and a glimmer of hope to PD treatment. This study school rehabilitation of Parkinson's disease in mice behavior, brain striatal dopamine and its metabolites 3,4 - dihydroxy phenylacetic acid (3,4-dihydroxyphenylacetic acid, DOPAC) and homovanillic acid (homovanillic acid, HVA ) levels in the substantia nigra tyrosine hydroxylase and glial fibrillary acidic protein, to explore rehabilitation training to improve motor function of Parkinson's disease in mice likelihood and mechanism. Method: 1. Specimen preparation: 96 healthy C57BL/6J male mice were randomly divided into normal group, sham operation group, model group and rehabilitation group, the normal group without any treatment, sham group after intraperitoneal injection of saline without any processing; model group and rehabilitation group intraperitoneal injection of 1 - methyl-4 - phenyl-1, 2,3,6 - tetrahydro-pyridine (1-Methyl-4-Phenyl-1 ,2,3,6-Tetrahydropyridine Preparation of PD Hrdrochloride, MPTP) mouse model after the success of the model group received no treatment, rehabilitation group underwent rehabilitation training, training a total of four weeks. 2 in rehabilitation training weeks, one week, two weeks and four weeks later were observed behavior of the mice learn to change, and at the same time cut at different times, different groups of mice brain tissue slices, using high-performance liquid chromatography detection mouse brain tissue DA and its metabolites content by immunohistochemical methods to detect changes in the expression of GFAP and TH, and data collection and analysis. Results: 1. 0 weeks after rehabilitation training, model group and rehabilitation mice limb function was significantly impaired, after two weeks of rehabilitation, the rehabilitation mice limb function improved significantly, the model mice raise obvious the two groups significant limb function in mice after four weeks of rehabilitation, the model group still improve is not obvious, the two groups compared significant differences. Model mice after two weeks of training in the rehabilitation of limb function compared with four weeks of rehabilitation training, no significant differences. 2 0 weeks after rehabilitation training, model group and rehabilitation mice striatum DA and its metabolites content was significantly reduced, a statistically significant difference compared with the normal group and sham group; rehabilitation after two weeks of training, the model group DA no significant change in its metabolites content the rehabilitation group DA and its metabolites were significantly improved, compared the two groups statistically significant difference; rehabilitation training four weeks after the DA and its metabolites content model group no noticeable increase and Rehabilitation group compared statistically different. Model mice after two weeks of training in the rehabilitation and after four weeks of rehabilitation training, brain DA and its metabolites content difference was not statistically significant. 3. Immunohistochemical staining showed no rehabilitation, model group and rehabilitation mice significantly reduced the number of TH-positive cells, a statistically significant difference compared with the normal group, sham group; after two weeks of rehabilitation, the rehabilitation group TH number of positive cells increased significantly, while the model group, no significant increase in the number of TH cells, the two groups there is a statistically significant difference; rehabilitation training after four weeks, the model of TH-positive cells increased obvious significant differences compared with the rehabilitation group. . Model mice after two weeks of training in the rehabilitation and after 4 weeks of rehabilitation, TH-positive cells was no significant difference. 4 0 weeks after rehabilitation, the normal group and sham-operated mice the visible small number of GFAP-positive cells in the model group and rehabilitation group GFAP number increased significantly, the difference was statistically significant compared with the normal group and sham group; model group with no significant difference in the rehabilitation group. Rehabilitation training after four weeks, the reduced model mice, GFAP-positive cells was not obvious, the rehabilitation group GFAP positive cells was significantly reduced, a significant difference compared with the model group. Model mice after two weeks of training in the rehabilitation and after 4 weeks of rehabilitation, GFAP positive cells was no significant difference. Conclusion: After the mice injected with MPTP Parkinson's disease behavior characteristics. Rehabilitation training can improve the the PD limb motor function of mice. 2. Rehabilitation training can be improved by increasing the brain content of dopamine and its metabolites the PD mouse limb function. Rehabilitation can increase the number of cells of Parkinson mouse brain TH, causing increased brain dopamine content and promote the recovery of neurological function, to improve the behavior of mice. Rehabilitation can reduce the activity of astrocytes, promote recovery of motor function in PD mice.

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