Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorders affecting close to 1% of the population worldwide over 65 year of age. It affects some 10 million people worldwide and about 40,000 in Taiwan. The annual prevalence rates of PD increased over the years, and there are no pharmacological treatments shown to have a significant, sustained capacity to prevent or attenuate the condition. Nowadays, mainstream PD treatment is via dopaminergic replacement therapy. However, standard pharmacotherapy is limited by progressive loss of efficacy and side effects develop with time. An additional preclinical study for testing novel treatment for PD is now needed. In this study, we will focus on evaluating the effect and molecular mechanism of exercise and deep brain stimulation (DBS) for PD. We hypothesize that exercise and DBS will increase the capacity of DA neurons to act on their postsynaptic targets by increasing NTF availability, improved mitochondrial function, and angiogenesis. We will use the preclinical rodent model MitoPark with a slow time course of dopaminergic neuroregeneration to evaluate the neuroprotective effects of exercise and DBS. The specific aims of this study are: (1) to determine the effects of exercise and DBS on dopaminergic function and mitochondria; (2) to explore the role of specific NTFs in exercise and DBS-induced protection of behavior and of dopaminergic activity; (3) to examine the role of angiogenesis in exercise and DBS-induced neuroprotection. We believe that the results of exercise and DBS in ameliorating histochemical, neurochemical, behavioral neural connectivity sequelae in PD mice will significantly advance the development of highly effective therapeutic methods for treating PD or other neurodegenerative disorders.
|Effective start/end date||8/1/18 → 7/1/19|
- Parkinson’s disease
- Deep brain stimulation