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The Journal of Neuroscience, May 16, 2007, 27(20):5291-5300; doi:10.1523/JNEUROSCI.1069-07.2007
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Neurobiology of Disease
Effects of Treadmill Exercise on Dopaminergic Transmission in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Lesioned Mouse Model of Basal Ganglia Injury
Giselle M. Petzinger,1,3 John P. Walsh,2 Garnik Akopian,2 Elizabeth Hogg,1 Avery Abernathy,1 Pablo Arevalo,1 Patty Turnquist,3 Marta Vu kovi
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Beth E. Fisher,3 Daniel M. Togasaki,1 andMichael W. Jakowec1,3 1Department of Neurology, 2Andrus Gerontology Center, and 3Department of Biokinesiology and Physical Therapy, The George and MaryLou Boone Center for Parkinson's Disease Research, University of Southern California, Los Angeles, California, 90033
Correspondence should be addressed to Dr. Michael W. Jakowec, Department of Neurology, University of Southern California, 1333 San Pablo Street, MCA-241, Los Angeles, CA 90033. Email: jakowec{at}surgery.usc.edu
Studies have suggested that there are beneficial effects of exercise in patients with Parkinson's disease, but the underlying molecular mechanisms responsible for these effects are poorly understood. Studies in rodent models provide a means to examine the effects of exercise on dopaminergic neurotransmission. Using intensive treadmill exercise, we determined changes in striatal dopamine in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse. C57BL/6J mice were divided into four groups: (1) saline, (2) saline plus exercise, (3) MPTP, and (4) MPTP plus exercise. Exercise was started 5 d after MPTP lesioning and continued for 28 d. Treadmill running improved motor velocity in both exercise groups. All exercised animals also showed increased latency to fall (improved balance) using the accelerating rotarod compared with nonexercised mice. Using HPLC, we found no difference in striatal dopamine tissue levels between MPTP plus exercise compared with MPTP mice. There was an increase detected in saline plus exercise mice. Analyses using fast-scan cyclic voltammetry showed increased stimulus-evoked release and a decrease in decay of dopamine in the dorsal striatum of MPTP plus exercise mice only. Immunohistochemical staining analysis of striatal tyrosine hydroxylase and dopamine transporter proteins showed decreased expression in MPTP plus exercise mice compared with MPTP mice. There were no differences in mRNA transcript expression in midbrain dopaminergic neurons between these two groups. However, there was diminished transcript expression in saline plus exercise compared with saline mice. Our findings suggest that the benefits of treadmill exercise on motor performance may be accompanied by changes in dopaminergic neurotransmission that are different in the injured (MPTP-lesioned) compared with the noninjured (saline) nigrostriatal system.
Key words: in situ hybridization; neurochemistry; neuroplasticity; substantia nigra; Parkinson's disease; tyrosine hydroxylase
Received Jan. 16, 2007; revised April 5, 2007; accepted April 7, 2007.
Correspondence should be addressed to Dr. Michael W. Jakowec, Department of Neurology, University of Southern California, 1333 San Pablo Street, MCA-241, Los Angeles, CA 90033. Email: jakowec{at}surgery.usc.edu
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