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
Open accessAbstract
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.
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Exercise has been shown to improve motor performance in MPTP and 6-OHDA models, including parkinsonian features.
“Exercise has been shown to improve motor performance in these models, including parkinsonian features 72–77.”
From Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease (2013) · cites this paper as [77]
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Cites
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859 · see citing works
The efficiency of systematic sampling in stereology and its prediction *
Gundersen, H., & Jensen, E. B. V. (1987) · Journal of Microscopy · doi:10.1111/j.1365-2818.1987.tb02837.x · Cited by 3,586 · see citing works
Day, B. L., Dressler, D. W., de Noordhout, A. M., MARSDEN, C. D., Nakashima, K., Rothwell, J. C., & Thompson, P. D. (1989) · The Journal of Physiology · doi:10.1113/jphysiol.1989.sp017626 · Cited by 932 · see citing works
Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity
Gómez-Pinilla, F., Ying, Z., Roy, R. R., Molteni, R., & Edgerton, V. R. (2002) · Journal of Neurophysiology · doi:10.1152/jn.00152.2002 · Cited by 724 · see citing works
Long-term synaptic depression in the striatum: physiological and pharmacological characterization
Calabresi, P., Maj, R., Pisani, A., Mercuri, N. B., & Bernardi, G. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-11-04224.1992 · Cited by 673 · see citing works
Jackson-Lewis, V. R., Jakowec, M. W., Burke, R. E., & Przedborski, S. (1995) · Neurodegeneration · doi:10.1016/1055-8330(95)90015-2 · Cited by 609 · see citing works
Self-citationRegulation of the vascular extracellular superoxide dismutase by nitric oxide and exercise training
Fukai, T., Siegfried, M. R., Ushio‐Fukai, M., Cheng, Y. C., Kojda, G., & Harrison, D. G. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9551 · Cited by 552 · see citing works
Molteni, R., Ying, Z., & Gómez‐Pinilla, F. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.02158.x · Cited by 441 · see citing works
Tillerson, J. L., Caudle, W. M., Reverón, M. E., & Miller, G. W. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00096-4 · Cited by 399 · see citing works
DAncing past the DAT at a DA synapse
Cragg, S. J., & Rice, M. E. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.03.011 · Cited by 373 · see citing works
Physical activity and the risk of Parkinson disease
Chen, H., Zhang, S. M., Schwarzschild, M. A., Hernán, M. A., & Ascherio, A. (2005) · Neurology · doi:10.1212/01.wnl.0000151960.28687.93 · Cited by 371 · see citing works
Forced Limb-Use Effects on the Behavioral and Neurochemical Effects of 6-Hydroxydopamine
Tillerson, J. L., Cohen, A. D., Philhower, J., Miller, G. W., Zigmond, M. J., & Schallert, T. J. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-12-04427.2001 · Cited by 357 · see citing works
Gainetdinov, R. R., Fumagalli, F., Jones, S. R., & Caron, M. G. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69031322.x · Cited by 353 · see citing works
Analysis of exocytotic events recorded by amperometry
Mosharov, E. V., & Sulzer, D. L. (2005) · Nature Methods · doi:10.1038/nmeth782 · Cited by 349 · see citing works
Fisher, B. E., Petzinger, G. M., Nixon, K., Hogg, E., Bremmer, S., Meshul, C. K., & Jakowec, M. W. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20162 · Cited by 311 · see citing works
Physical exercise induces FGF-2 and its mRNA in the hippocampus
Gómez‐Pinilla, F., Dao, L., & So, V. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00375-2 · Cited by 292 · see citing works
Neuroprotective effects of prior limb use in 6-hydroxydopamine-treated rats: possible role of GDNF
Cohen, A. D., Tillerson, J. L., Smith, A. D., Schallert, T., & Zigmond, M. J. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01657.x · Cited by 243 · see citing works
Environmental enrichment in adulthood eliminates neuronal death in experimental Parkinsonism
Faherty, C. J., Shepherd, K. R., Herasimtschuk, A., & Smeyne, R. J. (2004) · Molecular Brain Research · doi:10.1016/j.molbrainres.2004.08.008 · Cited by 241 · see citing works
Physical therapy and Parkinson's disease
Comelia, C. L., Stebbins, G. T., Brown-Toms, N., & Goetz, C. G. (1994) · Neurology · doi:10.1212/wnl.44.3_part_1.376 · Cited by 236 · see citing works
Bézard, E., Doveró, S., Belin, D., Duconger, S., Jackson-Lewis, V. R., Przedborski, S., Piazza, P. V., Gross, C. E., & Jaber, M. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-35-10999.2003 · Cited by 209 · see citing works
Kilpatrick, I. C., Jones, M. W., & Phillipson, O. T. (1986) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1986.tb08506.x · Cited by 195 · see citing works
Cragg, S. J., & Greenfield, S. A. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-15-05738.1997 · Cited by 184 · see citing works
Ricaurte, G. A., Langston, J. W., DeLanney, L. E., Irwin, I., Peroutka, S. J., & Forno, L. S. (1986) · Brain Research · doi:10.1016/0006-8993(86)90905-4 · Cited by 180 · see citing works
Increased dopamine release from striata of rats after unilateral nigrostriatal bundle damage
Zhang, W. Q., Tilson, H. A., Nanry, K. P., Hudson, P. M., Hong, J., & Stachowiak, M. K. (1988) · Brain Research · doi:10.1016/0006-8993(88)90264-8 · Cited by 148 · see citing works
Jaber, M., Dumartin, B., Sagné, C., Haycock, J. W., Roubert, C., Bruno Giros, A., Bloch, B., & Caron, M. G. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00764.x · Cited by 143 · see citing works
Kojda, G., Cheng, Y. C., Burchfield, J. S., & Harrison, D. G. (2001) · Circulation · doi:10.1161/01.cir.103.23.2839 · Cited by 143 · see citing works
Schulte, A., & Chow, R. H.-P. (1996) · Analytical Chemistry · doi:10.1021/ac960210n · Cited by 134 · see citing works
Ebrahimi-Gaillard, A., Pochet, R., & Roger, M. (1992) · Neuroscience Research · doi:10.1016/s0168-0102(05)80005-7 · Cited by 133 · see citing works
Chen, B. T., & Rice, M. E. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-19-07841.2001 · Cited by 129 · see citing works
Ouchi, Y. (2001) · Brain · doi:10.1093/brain/124.4.784 · Cited by 125 · see citing works
Fauchey, V., Jaber, M., Caron, M. G., Bloch, B., & Moine, C. L. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00876.x · Cited by 118 · see citing works
O’Dell, S. J., Gross, N. B., Fricks, A. N., Casiano, B. D., Nguyen, T. B., & Marshall, J. F. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2006.10.042 · Cited by 118 · see citing works
Garris, P. A., Walker, Q. D., & Wightman, R. M. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00003-6 · Cited by 111 · see citing works
Jakowec, M. W., Yen, L., & Kalb, R. G. (1995) · Neuroscience · doi:10.1016/0306-4522(95)00094-y · Cited by 104 · see citing works
Self-citationIrwin, I., Finnegan, K. T., DeLanney, L. E., Monte, D. A. D., & Langston, J. W. (1992) · Brain Research · doi:10.1016/0006-8993(92)90473-m · Cited by 95 · see citing works
Jakowec, M. W., Nixon, K., Hogg, E., McNeill, T., & Petzinger, G. M. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20114 · Cited by 90 · see citing works
Self-citationExercise affects glutamate receptors in postsynaptic densities from cortical mice brain
Dietrich, M. O., Mantese, C. E. A., Porciúncula, L. O., Ghisleni, G., Vinadé, L., Souza, D. O., & Portela, L. V. (2005) · Brain Research · doi:10.1016/j.brainres.2005.09.038 · Cited by 84 · see citing works
Metabolic mapping of rat striatum: somatotopic organization of sensorimotor activity
Brown, L. L., & Sharp, F. R. (1995) · Brain Research · doi:10.1016/0006-8993(95)00457-2 · Cited by 82 · see citing works
Nguyen, P. T., Holschneider, D. P., Maarek, J. I., et al. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.05.014 · Cited by 62 · see citing works
Synaptic organization of motor corticostriatal projections in the rat
Cospito, J. A., & Kultas‐Ilinsky, K. (1981) · Experimental Neurology · doi:10.1016/0014-4886(81)90221-1 · Cited by 60 · see citing works
Burke, R. E., Cadet, J. L., Kent, J. D., Karanas, A. L., & Jackson-Lewis, V. R. (1990) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(90)90095-w · Cited by 59 · see citing works
Yavich, L., & MacDonald, E. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02403-3 · Cited by 57 · see citing works
Functional Brain Mapping in Freely Moving Rats during Treadmill Walking
Holschneider, D. P., Maarek, J.-M. I., Yang, J., Harimoto, J., & Scremin, O. U. (2003) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/01.wcb.0000072797.66873.6a · Cited by 51 · see citing works
Regional differences in the expression of corticostriatal synaptic plasticity
Smith, R. B., Musleh, W., Akopian, G. K., Buckwalter, J. G., & Walsh, J. P. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00260-3 · Cited by 44 · see citing works
Self-citationPetzinger, G. M., Fisher, B. E., Hogg, E., Abernathy, A., Arevalo, P., Nixon, K., & Jakowec, M. W. (2005) · Journal of Neuroscience Research · doi:10.1002/jnr.20730 · Cited by 41 · see citing works
Self-citationDentresangle, C., Cavorsin, M. L., Savasta, M., et al. (2001) · Brain Research · doi:10.1016/s0006-8993(00)03311-4 · Cited by 39 · see citing works
SPECT tracer [123I]IBZM has similar affinity to dopamine D2 and D3 receptors
Videb�k, C., Toska, K., Scheideler, M. A., Paulson, O. B., & Knudsen, G. M. (2000) · Synapse · doi:10.1002/1098-2396(20001201)38:3 · Cited by 38 · see citing works
Miles, P. R., Mundorf, M. L., & Wightman, R. M. (2002) · Synapse · doi:10.1002/syn.10069 · Cited by 38 · see citing works
Foroud, T. (2005) · Neurology · doi:10.1212/01.wnl.0000179342.58181.c9 · Cited by 34 · see citing works
Akopian, G. K., & Walsh, J. P. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2006.115790 · Cited by 19 · see citing works
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Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease
Petzinger, G. M., Fisher, B. E., McEwen, S., Beeler, J. A., Walsh, J. P., & Jakowec, M. W. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70123-6 · Cited by 798 · see citing works
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Mattson, M. P., Moehl, K., Ghena, N., Schmaedick, M., & Cheng, A. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.156 · Cited by 624 · see citing works
Fisher, B. E., Wu, A. D., Salem, G. J., Song, J., Lin, C.-H. (., Yip, J., Cen, S., Gordon, J., Jakowec, M., & Petzinger, G. (2008) · Archives of Physical Medicine and Rehabilitation · doi:10.1016/j.apmr.2008.01.013 · Cited by 474 · see citing works
Self-citationDoes vigorous exercise have a neuroprotective effect in Parkinson disease?
Ahlskog, J. E. (2011) · Neurology · doi:10.1212/wnl.0b013e318225ab66 · Cited by 463 · see citing works
Energy intake and exercise as determinants of brain health and vulnerability to injury and disease
Mattson, M. P. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.08.012 · Cited by 434 · see citing works
Mirelman, A., Maidan, I., Herman, T., Deutsch, J. E., Giladi, N., & Hausdorff, J. M. (2011) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glq201 · Cited by 418 · see citing works
Exercise Benefits Brain Function: The Monoamine Connection
Lin, T.-W., & Kuo, Y.-M. (2013) · Brain Sciences · doi:10.3390/brainsci3010039 · Cited by 392 · see citing works
Physical activities and future risk of Parkinson disease
Xu, Q., Park, Y., Huang, X., Hollenbeck, A., Blair, A., Schatzkin, A., & Chen, H. (2010) · Neurology · doi:10.1212/wnl.0b013e3181ea1597 · Cited by 328 · see citing works
Neuroplasticity of Dopamine Circuits After Exercise: Implications for Central Fatigue
Foley, T. E., & Fleshner, M. (2008) · NeuroMolecular Medicine · doi:10.1007/s12017-008-8032-3 · Cited by 261 · see citing works
Fisher, B. E., Li, Q., Nacca, A., Salem, G. J., Song, J., Yip, J., Hui, J. S., Jakowec, M. W., & Petzinger, G. M. (2013) · Neuroreport · doi:10.1097/wnr.0b013e328361dc13 · Cited by 247 · see citing works
Wu, S.-Y., Wang, T.-F., Yu, L., Jen, C. J., Chuang, J.-I., Wu, F.-S., Wu, C.-W., & Kuo, Y.-M. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.09.006 · Cited by 206 · see citing works
Herman, T., Giladi, N., & Hausdorff, J. M. (2009) · Journal of Neural Transmission · doi:10.1007/s00702-008-0139-z · Cited by 193 · see citing works
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Alberts, J. L., Linder, S. M., Penko, A. L., Lowe, M. J., & Phillips, M. (2011) · Exercise and Sport Sciences Reviews · doi:10.1097/jes.0b013e31822cc71a · Cited by 192 · see citing works
Hirsch, M. A., van Wegen, E. E. H., Newman, M. A., & Heyn, P. C. (2018) · Translational Neurodegeneration · doi:10.1186/s40035-018-0112-1 · Cited by 134 · see citing works
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Zigmond, M. J., Cameron, J. L., Leak, R. K., Mirnics, K., Russell, V. A., Smeyne, R. J., & Smith, A. D. (2009) · Parkinsonism & Related Disorders · doi:10.1016/s1353-8020(09)70778-3 · Cited by 121 · see citing works
Gorton, L. M., Vuckovic, M. G., Vertelkina, N., Petzinger, G. M., Jakowec, M. W., & Wood, R. I. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.05.009 · Cited by 112 · see citing works
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VanLeeuwen, J., Petzinger, G. M., Walsh, J. P., Akopian, G. K., Vuckovic, M., & Jakowec, M. W. (2010) · Journal of Neuroscience Research · doi:10.1002/jnr.22216 · Cited by 94 · see citing works
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Davies, J. M. S., Cillard, J., Friguet, B., Cadenas, E., Cadet, J., Cayce, R., Fishmann, A., Liao, D., Bulteau, A.-L., Derbré, F., et al. (2017) · GeroScience · doi:10.1007/s11357-017-0002-y · Cited by 82 · see citing works
Self-citationHalperin, J. M., Berwid, O. G., & O’Neill, S. (2014) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2014.05.005 · Cited by 75 · see citing works
Smith, B. A., Goldberg, N. R. S., & Meshul, C. K. (2011) · Brain Research · doi:10.1016/j.brainres.2011.02.003 · Cited by 67 · see citing works
Patten, A. R., Yau, S. Y., Fontaine, C. J., Meconi, A., Wortman, R. C., & Christie, B. R. (2015) · Brain Plasticity · doi:10.3233/bpl-150016 · Cited by 64 · see citing works
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- Authors
- Petzinger, G. M., Walsh, J. P., Akopian, G., Hogg, E., Abernathy, A., Arevalo, P., Turnquist, P., Vučković, M., Fisher, B. E., Togasaki, D. M., & Jakowec, M. W.
- Affiliations
- University of Southern California (US)
- Corresponding author
- Jakowec, Michael W.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-05-16
- Volume
- 27
- Issue
- 20
- Pages
- 5291-5300
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6672356
- OpenAlex
- W2078238654
- Cited by
- 329
- References
- 50
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 16 · 2023: 7 · 2022: 14 · 2021: 16 · 2020: 18 · 2019: 18 · 2018: 20 · 2017: 18 · 2016: 20 · 2015: 20 · 2014: 18 · 2013: 30 · 2012: 20
- FWCI
- 10.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Parkinson's Disease Foundation
- University of Southern California
- U.S. Army (W81XWH)
- National Institute of Neurological Disorders and Stroke (R01NS044327, R01 NS44327-1)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- treadmill exercise, dopamine signaling, MPTP lesion, Parkinson's disease, basal ganglia lesions, striatal dopamine, nigrostriatal pathway, tyrosine hydroxylase, dopamine transporter, motor performance, exercise therapy
- MeSH terms
- Animals, Basal Ganglia, Disease Models, Animal, Dopamine, Exercise Therapy, Male, Mice, Inbred C57BL, Motor Activity, Synaptic Transmission, Parkinson Disease, MPTP Poisoning, Mice
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