Increasing Endogenous Neurogenesis Using Neurosteroids: A Novel Therapeutic Strategy to Treat Parkinson's Disease

Objective/Rationale: 
We will test a locally produced brain chemical that increases the generation of new neurons to replace the damaged neurons in Parkinson disease (PD). The production of this chemical is reduced in aging and diseased brains. Promising results have been obtained that this chemical increases the generation of new neurons and reverses the deficits of cognitive function in a pre-clinical model of Alzheimer’s disease. In this study, we will test its effects in a pre-clinical model of PD. 

Project Description: 
The project has four goals: 

1. To determine its efficacy on production of new neurons;
2. To determine its efficacy on migration and survival of new neurons;
3. To determine its efficacy on augmentation of dopamine (the key neurotransmitter in PD) levels in brain regions which play key roles in PD;
4. To determine its efficacy on rescuing the movement deficits in PD pre-clinical models.

The study will use automated three-dimensional analysis to count the newly formed cells which are labeled by a proliferating marker. The characteristic of the new cells will be identified by double or triple immunohistochemical assay. Serial brain sections will be used to track the path of migration and the destination of the newly formed cells.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:  
This pilot project is designed to obtain proof of concept evidence for development of a novel drug as a treatment for Parkinson’s disease.

Anticipated Outcome: 
We anticipate that this chemical will reduce the movement disorders, increase the formation, migration, and survival of the number of dopamine producing cells in brain of PD pre-clinical models. Positive results from any or all of these measurements will be important in anti-PD drug development.