Pharmacoligcal and Behavioral Enhancement of Neuroplasticity in the MPTP-Lesioned Mouse and Non-Human Primate
Abstract
The purpose of this proposal is to investigate the molecular mechanisms involving pharmacological and behavioral (exercise) enhanced neuroplasticity of the injured basal ganglia. Our central hypothesis is that exercise and pharmacological intervention specifically the administration of a D2 dopamine receptor agonist enhances neuroplasticity by modulating glutamate-dopamine interactions. The following proposal has two complementary components using two animal models to address the molecular mechanisms underlying exercise- and pharmacologically-enhanced neuroplasticity. Using the MPTP C57BL/6 mouse Component One will test the hypothesis that exercise enhances plasticity of the MPTP-injured basal ganglia through glutamate by modulating dopamine biosynthesis. This hypothesis will be tested through changes in dopamine, and proteins involved in dopamine biosynthesis and uptake (tyrosine hydroxylase and dopamine transporter) and changes in glutamatergic synapses and receptor subtype. This hypothesis will be further tested through determining whether exercise-enhanced neuroplasticity may be attenuated with a glutamate antagonist. Using the MPTP lesioned non-human primate Component Two will test the hypothesis that the administration of a D2 receptor agonist (Pramipexole) enhances neuroplasticity of the MPTP-injured basal ganglia through its effect on pre- and post-synaptic dopamine biosynthesis, uptake and receptor expression as well as glutamatergic synapses. This hypothesis will be tested through changes in dopamine and its metabolites, proteins involved in dopamine biosynthesis, uptake, and storage (tyrosine hydroxylase, dopamine transporter, and vesicular monoamine transporter), changes in dopamine receptor subtypes and their respective neuropeptides, and changes in glutamatergic synapses.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2005
- Accession Number
- ADA436902
Entities
People
- Giselle M. Petzinger
- Michael W. Jakowec
Organizations
- University of Southern California