Accession Number:

ADA456048

Title:

Pharmacological and Behavioral Enhancement of Neuroplasticity in the MPTP-Lesioned Mouse and Nonhuman Primate

Descriptive Note:

Annual rept. 1 May 2005-30 Apr 2006

Corporate Author:

UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES

Personal Author(s):

Report Date:

2006-05-01

Pagination or Media Count:

60.0

Abstract:

The purpose of this proposal is to investigate the mechanisms involving pharmacological and behavioral 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 glutamatedopamine interactions. This proposal has two components. Using the MPTP C57BL6 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 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 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.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research
  • Organic Chemistry

Distribution Statement:

APPROVED FOR PUBLIC RELEASE