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Neuroplasticity in the MPTP‐Lesioned Mouse and Nonhuman Primate
Author(s) -
JAKOWEC MICHAEL W.,
FISHER BETH,
NIXON KERRY,
HOGG ELIZABETH,
MESHUL CHARLES,
BREMMER SAMUEL,
McNEILL TOM,
PETZINGER GISELLE M.
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2003.tb07489.x
Subject(s) - medicine , gerontology
: 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 glutamate-dopamine interactions. This proposal has two components. 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 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.