Can the brain be protected through exercise? Lessons from an animal model of parkinsonism☆
Abstract
Evidence suggests that following injury the brain has the capacity for self-repair and that this can be promoted through a variety of experiences including motor activity. In their article, Döbrössy and Dunnett have provided further evidence that this is the case in an animal model in which an excitotoxin is applied to the neostriatum. Under standard conditions, such a toxin would cause considerable damage to the GABAergic cells of this region and produce behavioral deficits. This model has been used to explore certain aspects of Huntington's disease, which also involves the loss of these neurons. However, Döbrössy and Dunnett show that the damage can be reduced by prior motor training. We have been exploring the neuroprotective effects of motor exercise in a different model, one involving 6-hydroxydopamine, which normally destroys dopamine neurons. Our results indicate that forced exercise can reduce the vulnerability of dopamine neurons to 6-hydroxydopamine. The results further suggest that this protection is due in part to an increase in the availability of the trophic factor GDNF, which can in turn stimulate certain signaling cascades, including one that activates ERK. Our results, together with those of Döbrössy and Dunnett and others, raise the possibility that exercise will protect against a variety of neurodegenerative conditions.
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Exercise raises neurotrophic factors that are neuroprotective, promote cell and neuron growth, and produce synaptic plasticity.
“exercise increases levels of neurotrophic factors that have been shown to be neuroprotective, to enhance cell and neuron growth, and to engender synaptic plasticity”
From Enrichment Effects on Adult Cognitive Development: Can the Functional Capacity of Older Adults Be Preserved and Enhanced? (2008) · cites this paper as Smith & Zigmond, 2003
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Vidal-Martínez, G., Segura‐Ulate, I., Yang, B. C., Diaz-Pacheco, V., Barragan, J. A., Esquivel, J. D.-L., Chaparro, S. A., Vargas‐Medrano, J., & Perez, R. G. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.113120 · Cited by 26 · see citing works
Analysis of viral and genetic factors in South African patients with multiple sclerosis
de Villiers, J. N. P., Treurnicht, F. K., Warnich, L., Carr, J. A., van Rensburg, S. J., & Kotze, M. J. (2006) · Metabolic Brain Disease · doi:10.1007/s11011-006-9016-3 · Cited by 26 · see citing works
Ciucci, M. R., Schaser, A. J., & Russell, J. A. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.06.004 · Cited by 24 · see citing works
- Authors
- Smith, A. D., & Zigmond, M. J.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Zigmond, Michael J
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2003-11
- Volume
- 184
- Issue
- 1
- Pages
- 31-39
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W2065546153
- Cited by
- 209
- References
- 119
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 2 · 2022: 7 · 2021: 4 · 2020: 6 · 2019: 6 · 2018: 5 · 2017: 10 · 2016: 4 · 2015: 8 · 2014: 6 · 2013: 18 · 2012: 10
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Michael J. Fox Foundation for Parkinson's Research
- National Institutes of Health (5r01ns039267-05, 5r21ns043701-02)
- National Institute of Mental Health (MH-29670)
- National Institute of Neurological Disorders and Stroke (NS 19608, NS39267, NS43701)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- physical activity, neuroprotection, parkinsonism, 6-hydroxydopamine, dopaminergic neurons, glial cell line-derived neurotrophic factor, ERK signaling, motor training, excitotoxicity, neostriatum, neurodegeneration
- MeSH terms
- Animals, Physical Exertion, Humans, Nerve Growth Factors, Synaptic Transmission, Parkinson Disease, Secondary, Physical Conditioning, Animal, Sympatholytics, Oxidopamine, Glial Cell Line-Derived Neurotrophic Factor
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