Exercise does not protect against MPTP-induced neurotoxicity in BDNF happloinsufficent mice
Open accessAbstract
Exercise has been demonstrated to potently protect substantia nigra pars compacta (SN) dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. One mechanism proposed to account for this neuroprotection is the upregulation of neurotrophic factors. Several neurotrophic factors, including Brain Derived Neurotrophic Factor (BDNF), have been shown to upregulate in response to exercise. In order to determine if exercise-induced neuroprotection is dependent upon BDNF, we compared the neuroprotective effects of voluntary exercise in mice heterozygous for the BDNF gene (BDNF+/-) with strain-matched wild-type (WT) mice. Stereological estimates of SNpc DA neurons from WT mice allowed 90 days exercise via unrestricted running demonstrated complete protection against the MPTP-induced neurotoxicity. However, BDNF+/- mice allowed 90 days of unrestricted exercise were not protected from MPTP-induced SNpc DA neuron loss. Proteomic analysis comparing SN and striatum from 90 day exercised WT and BDNF+/- mice showed differential expression of proteins related to energy regulation, intracellular signaling and trafficking. These results suggest that a full genetic complement of BDNF is critical for the exercise-induced neuroprotection of SNpc DA neurons.
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Heterozygous deletion of the BDNF gene (Bdnf+/− mice) led to a lack of exercise-induced dopaminergic neuroprotection.
“Gerecke et al. [143] reported that heterozygous deletion of the BDNF gene (Bdnf+/− mice) led to a lack of exercise-induced dopaminergic neuroprotection.”
From BDNF as a Promising Therapeutic Agent in Parkinson’s Disease (2020) · cites this paper as [143]
Exercise initiated one week post-toxin administration fails to protect from cell death.
“For example exercise initiated one week post-toxin administration fails to protect from cell death 82.”
From Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease (2013) · cites this paper as [82]
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Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease
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Self-citation
- Authors
- Gerecke, K. M., Jiao, Y., Pagala, V., & Smeyne, R. J.
- Affiliations
- Rhodes College (US)
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Gerecke, Kim M.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-08-17
- Volume
- 7
- Issue
- 8
- Pages
- e43250
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3422268
- OpenAlex
- W2017014342
- Cited by
- 53
- References
- 139
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 6 · 2018: 7 · 2017: 5 · 2016: 4 · 2015: 7 · 2014: 6 · 2013: 4
- FWCI
- 3.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- American Lebanese Syrian Associated Charities
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS070825, R01NS039006, NS039006)
- 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, MPTP-induced neurotoxicity, substantia nigra pars compacta, dopaminergic neurons, neuroprotection, neurotrophic factors, voluntary running, striatum, protein expression, Parkinson's disease model
- MeSH terms
- Animals, Electrophoresis, Agar Gel, Genotype, Immunohistochemistry, Physical Conditioning, Animal, Substantia Nigra, DNA Primers, Brain-Derived Neurotrophic Factor, MPTP Poisoning, Proteomics, Mice, Tandem Mass Spectrometry, Haploinsufficiency, Dopaminergic Neurons
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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