Mechanisms of Striatal Neuroplasticity That Ameliorate the Motor Impairments in Parkinson s Disease
Abstract
Parkinson?s disease is a debilitating neurodegenerative disorder characterized by the loss of dopamine neurons in the substantia nigra pars compacta, which produces tremor, rigidity, bradykinesia, and postural instability. No therapies exist that halt the progression of the disease, and therapies to alleviate the motor symptoms remain inadequate. The gold standard treatment remains the systemic administration of the dopamine precursor, L-3,4-dihydroxyphenylalanine, which increases the levels of dopamine. However, with prolonged use the drug often loses effectiveness or produces unwanted movements known as dyskinesias that delay its use. Our group recently showed that mice lacking the vesicular glutamate transporter 3 do not develop the motor impairments normally induced in models of Parkinson?s disease. We hypothesize that previously unappreciated forms of striatal neuroplasticity correct or compensate for the deleterious changes in motor output that normally result from the loss of dopamine. The goal of this Parkinson s Research Program Focused Idea Award proposal is to identify and characterize the novel neuroplasticity mechanisms that underlie preserved motor function in the knockout animals. Our ultimate goal is to use insights from these studies to develop new therapeutic strategies to treat motor and other related symptoms of Parkinson?s disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710386
Entities
People
- Rebecca P Seal
Organizations
- United States Army
- University of Pittsburgh