Neuroprotective effects and mechanisms of exercise in a chronic mouse model of Parkinson’s disease with moderate neurodegeneration: Exercise neuroprotection in chronic parkinsonism
Open accessAbstract
The protective impact of exercise on neurodegenerative processes has not been confirmed, and the mechanisms underlying the benefit of exercise have not been determined in human Parkinson's disease or in chronic animal disease models. This research examined the long-term neurological, behavioral, and mechanistic consequences of endurance exercise in experimental chronic parkinsonism. We used a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease with moderate neurodegeneration and examined the effects of treadmill exercise on movement and balance coordination, changes in dopamine neuron biomarkers, mitochondrial functions, and neurotrophic factor activities in the nigrostriatal system. The exercise results were compared with those of the control and sedentary chronic parkinsonian animals. After 18 weeks of exercise training in the chronic parkinsonian mice, we observed a significant deterrence in the loss of neuronal dopamine-producing cells and other functional indicators. The impaired movement and balance incoordination in the chronic parkinsonian mice were also markedly reduced following exercise. Mechanistic investigations revealed that the neuronal and behavioral recovery produced by exercise in the chronic parkinsonian mice was associated with an improved mitochondrial function and an increase in the brain region-specific levels of brain-derived and glial cell line-derived neurotrophic factors. Our findings indicate that exercise not only produces neuronal and mitochondrial protection, it also boosts nigrostriatal neurotrophic factor levels in the chronic parkinsonian mice with moderate neurodegeneration. Therefore, modifying lifestyle with increased exercise activity would be a non-pharmacological neuroprotective approach for averting neurodegenerative processes, as demonstrated in experimental chronic parkinsonism.
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BDNF upregulation due to exercise was observed in midbrain, substantia nigra, striatum, hippocampus, and cortex.
“BDNF upregulation was observed in midbrain [125], SN [126,128,129], ST [127,129,131,133], hippocampus [133], and cortex [132,133].”
From BDNF as a Promising Therapeutic Agent in Parkinson’s Disease (2020) · cites this paper as [126]
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- Authors
- Lau, Y.-S., Patki, G., Das-Panja, K., Le, W.-D., & Ahmad, S. O.
- Affiliations
- University of Houston (US)
- University of Kansas Medical Center (US)
- ORCID
- Ahmad, S. Omar
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2011-03-07
- Volume
- 33
- Issue
- 7
- Pages
- 1264-1274
- ISSN
- 0953-816X (ISSN-L)
- PMC
- PMC3079264
- OpenAlex
- W1800951710
- Cited by
- 275
- References
- 51
- Citations by year
- 2026: 5 · 2025: 16 · 2024: 19 · 2023: 11 · 2022: 14 · 2021: 18 · 2020: 20 · 2019: 18 · 2018: 16 · 2017: 25 · 2016: 21 · 2015: 28 · 2014: 20 · 2013: 16 · 2012: 19
- FWCI
- 13.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS47920, R01NS047920)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- Parkinson's disease, physical activity, neuroprotection, MPTP, treadmill exercise, dopaminergic neurons, mitochondrial function, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, nigrostriatal pathway, motor coordination, balance, non-pharmacological treatment
- MeSH terms
- Adjuvants, Pharmaceutic, Animals, Corpus Striatum, Disease Models, Animal, Dopamine, Humans, Male, Mice, Inbred C57BL, Mitochondria, Motor Activity, Nerve Degeneration, Neurons, Parkinson Disease, Physical Conditioning, Animal, Probenecid, Substantia Nigra, Superoxide Dismutase, Biomarkers, Exercise, Brain-Derived Neurotrophic Factor, Parkinsonian Disorders, Glial Cell Line-Derived Neurotrophic Factors, Mice
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