Exercise-induced behavioral recovery and neuroplasticity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse basal ganglia
Abstract
Physical activity has been shown to be neuroprotective in lesions affecting the basal ganglia. Using a treadmill exercise paradigm, we investigated the effect of exercise on neurorestoration. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model provides a means to investigate the effect of exercise on neurorestoration because 30-40% of nigrostriatal dopaminergic neurons survive MPTP lesioning and may provide a template for neurorestoration to occur. MPTP-lesioned C57 BL/6J mice were administered MPTP (four injections of 20 mg/kg free-base, 2 hr apart) or saline and divided into the following groups: (1). saline; (2). saline + exercise; (3). MPTP; and (4) MPTP + exercise. Mice in exercise groups were run on a motorized treadmill for 30 days starting 4 days after MPTP lesioning (a period after which MPTP-induced cell death is complete). Initially, MPTP-lesioned + exercise mice ran at slower speeds for a shorter amount of time compared to saline + exercise mice. Both velocity and endurance improved in the MPTP + exercise group to near normal levels over the 30-day exercise period. The expression of proteins and genes involved in basal ganglia function including the dopamine transporter (DAT), tyrosine hydroxylase (TH), and the dopamine D1 and D2 receptors, as well as alterations on glutamate immunolabeling were determined. Exercise resulted in a significant downregulation of striatal DAT in the MPTP + exercise compared to MPTP nonexercised mice and to a lesser extent in the saline + exercised mice compared to their no-exercise counterparts. There was no significant difference in TH protein levels between MPTP and MPTP + exercise groups at the end of the study. The expression of striatal dopamine D1 and D2 receptor mRNA transcript was suppressed in the saline + exercise group; however, dopamine D2 transcript expression was increased in the MPTP + exercise mice. Immunoelectron microscopy indicated that treadmill exercise reversed the lesioned-induced increase in nerve terminal glutamate immunolabeling seen after MPTP administration. Our data demonstrates that exercise promotes behavioral recovery in the injured brain by modulating genes and proteins important to basal ganglia function.
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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 [76]
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- Authors
- Fisher, B. E., Petzinger, G. M., Nixon, K., Hogg, E., Bremmer, S., Meshul, C. K., & Jakowec, M. W.
- Affiliations
- University of Southern California (US)
- Oregon Health & Science University (US)
- Corresponding author
- Jakowec, Michael W.
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2004-05-20
- Volume
- 77
- Issue
- 3
- Pages
- 378-390
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- OpenAlex
- W2084445735
- Cited by
- 311
- References
- 41
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 7 · 2023: 6 · 2022: 10 · 2021: 19 · 2020: 20 · 2019: 14 · 2018: 19 · 2017: 13 · 2016: 13 · 2015: 21 · 2014: 13 · 2013: 29 · 2012: 15
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS044327, R01 NS44327-1)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- physical activity, neuroplasticity, neurorestoration, MPTP lesion, basal ganglia, Parkinson's disease model, dopamine transporter, dopamine D1 receptor, dopamine D2 receptor, tyrosine hydroxylase, striatum, treadmill running, behavioral recovery, neuroprotection, gene expression changes, C57BL/6J mice, dopaminergic neurons
- MeSH terms
- Animals, Basal Ganglia, Behavior, Animal, Male, Membrane Glycoproteins, Mice, Inbred C57BL, Nerve Tissue Proteins, Neuronal Plasticity, Physical Conditioning, Animal, Tyrosine 3-Monooxygenase, MPTP Poisoning, Membrane Transport Proteins, Dopamine Plasma Membrane Transport Proteins, Mice
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