ArticleNeuroscience2015
HIF1α is necessary for exercise-induced neuroprotection while HIF2α is needed for dopaminergic neuron survival in the substantia nigra pars compacta.
Article in Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed.
- Hypoxic conditioning in Parkinson's disease: randomized controlled multiple N-of-1 trials.Nature communications · 2025Trial
- Increased oxygen demand during exercise as a stimulus for neuroprotection: A working hypothesis.Neural regeneration research · 2026Article
- Reduced microvascular coverage links a hypoxia-associated niche to microglial autophagic dysfunction in Parkinson's disease.Acta neuropathologica communications · 2026Article
- Review
- Exercise and smoking: health rivals revealing shared protective mechanisms in Parkinson's?NPJ Parkinson's disease · 2026Review
- Dopamine-endocannabinoid crosstalk drives exercise-induced bidirectional plasticity in Parkinson's disease.NPJ Parkinson's disease · 2026Article
- Neurobiology of exercise in Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Juggling Under Controlled Hypoxia as a Multimodal Coordinative and Cognitive Training in Parkinson's Disease-A Narrative Review.Journal of functional morphology and kinesiology · 2026Review
- Combining exercise and hypoxia for brain health: from elite athlete altitude training camps to clinical applications.AIMS neuroscience · 2026Review
- Restoring NADFrontiers in nutrition · 2026Review
- Lactate-induced metabolic signaling is the potential mechanism for reshaping the brain function - role of physical exercise.Frontiers in endocrinology · 2025Review
- Neuroprotection of low dose carbon monoxide in Parkinson's disease models commensurate with the reduced risk of Parkinson's among smokers.NPJ Parkinson's disease · 2024Article
- New Aspects Regarding the Fluorescence Spectra of Melanin and Neuromelanin in Pigmented Human Tissue Concerning Hypoxia.International journal of molecular sciences · 2024Article
- Randomized controlled trial of intermittent hypoxia in Parkinson's disease: study rationale and protocol.BMC neurology · 2024Article
- The Normobaric Oxygen Paradox-Hyperoxic Hypoxic Paradox: A Novel Expedient Strategy in Hematopoiesis Clinical Issues.International journal of molecular sciences · 2022Review
- Article
- Exercise training ameliorates cognitive dysfunction in amyloid beta-injected rat model: possible mechanisms of Angiostatin/VEGF signaling.Metabolic brain disease · 2021Article
- Review
- Cell Type-Specific Oxidative Stress Genomic Signatures in the Globus Pallidus of Dopamine-Depleted Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Pharmacological enrichment of polygenic risk for precision medicine in complex disorders.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Exercise reduces the risk of developing a number of neurological disorders and increases the efficiency of cellular energy production. However, overly strenuous exercise produces oxidative stress. Proper oxygenation is crucial for the health of all tissues, and tight regulation of cellular oxygen is critical to balance O2 levels and redox homeostasis in the brain. Hypoxia Inducible Factor (HIF)1α and HIF2α are transcription factors regulated by cellular oxygen concentration that initiate gene regulation of vascular development, redox homeostasis, and cell cycle control. HIF1α and HIF2α contribute to important adaptive mechanisms that occur when oxygen and ROS homeostasis become unbalanced. It has been shown that preconditioning by exposure to a stressor prior to a hypoxic event reduces damage that would otherwise occur. Previously we reported that 3 months of exercise protects SNpc dopaminergic (DA) neurons from toxicity caused by Complex I inhibition. Here, we identify the cells in the SNpc that express HIF1α and HIF2α and show that running exercise produces hypoxia in SNpc DA neurons, and alters the expression of HIF1α and HIF2α. In mice carrying a conditional knockout of Hif1α in postnatal neurons we observe that exercise alone produces SNpc TH+ DA neuron loss. Loss of HIF1α also abolishes exercise-induced neuroprotection. In mice lacking Hif2α in postnatal neurons, the number of TH+ DA neurons in the adult SNpc is diminished, but 3months of exercise rescues this loss. We conclude that HIF1α is necessary for exercise-induced neuroprotection and both HIF1α and HIF2α are necessary for the survival and function of adult SNpc DA neurons.
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