Study Rationale: Parkinson’s disease is a common neurodegenerative disorder that is usually diagnosed in people between 60 and 65 years old, but it likely starts about 20 years earlier. During this early stage, the disease is hard to diagnose because it can cause many different symptoms. Some of the early changes include vocalizations and the way individuals move. This study evaluates Parkinson-like symptoms in two types of Pink1-/- genetic pre-clinical models. These models have a genetic deletion that causes an early-onset form of the disease. These models are useful research tools because they can be used as a model of the disease, they allow researchers to ask questions that are impossible to study in humans. The goal of this work is to see how helpful these models are for scientists who are studying the early stage of Parkinson’s disease, before it is officially diagnosed.
Hypothesis: We hypothesize that the CRISPR Pink1-/- pre-clinical model might show signs of Parkinson’s disease that are similar to what happens in humans, including changes to vocalization and movement, and that these signs may appear at a young age, and progress. We also hypothesize that this model will have clear and consistent changes in the brainstem, the part of the brain where the disease likely begins, that more closely match the early stages of Parkinson’s in humans.
Study Design: We will study both the original Pink1-/- model and the newer Pink1-/- model made with a CRISPR technology. These models come from two different strains, Long Evans and Sprague Dawley, and we will include both males and females. In the laboratory, we will test their vocalizations and movement using common rat behavior tests. We will also measure dopamine levels and aggregated protein in their brains. These tests are often used to study Parkinson’s disease in rats and to make inferences to humans.
Impact on Diagnosis/Treatment of Parkinson’s disease: Findings from these studies will allow researchers to access comparative behavioral and brain data that will inform their future study designs using the Pink1-/- pre-clinical model.
Next Steps for Development: This work is valuable because it will provide direct behavioral and brain comparisons between Pink1-/- pre-clinical models that are used in biomedical research studies. This study includes female Pink1-/- pre-clinical models which increase the rigor, generalizability and translatability of the research findings to humans. Ultimately, this allows researchers to select a pre-clinical model of Parkinson disease to identify critical gaps in our understanding and move the field forward.