August 5, 2025Open Access

Hypoxia ameliorates neurodegeneration and movement disorder in a mouse model of Parkinson’s disease

EMEizo MarutaniHarvard University MMMaría MirandaBroad Institute TDTimothy DurhamBroad Institute

Key Points

Hypoxia prevents neurodegeneration and movement disorders caused by α-syn aggregates in mice with Parkinson's disease.
Elevated oxygen levels resulted in lipid peroxidation and DA neurodegeneration, while hypoxia provided neuroprotection.
Neuroprotective effects of hypoxia were noted in both mouse models and Caenorhabditis elegans, underscoring its broader relevance.
Initiating hypoxia after symptom onset reversed motor dysfunction, indicating potential therapeutic implications for Parkinson's disease.],
simple_explanation
Hypoxia is a low-oxygen environment that can protect brain cells. In Parkinson's disease, harmful proteins called α-synuclein build up and cause problems. Researchers found that exposing mice to hypoxia improved their movement and protected their brain cells even after symptoms started. This means that hypoxia could be a potential treatment to help people with Parkinson's disease feel better. 🌬️

Abstract

Abstract Parkinson’s disease (PD) is characterized by inclusions of α-synuclein (α-syn) and mitochondrial dysfunction in dopaminergic (DA) neurons of the substantia nigra pars compacta (SNpc). Patients with PD anecdotally experience symptom improvement at high altitude; chronic hypoxia prevents the development of Leigh-like brain disease in mice with mitochondrial complex I deficiency. Here we report that intrastriatal injection of α-syn preformed fibrils (PFFs) in mice resulted in neurodegeneration and movement disorder, which were prevented by continuous exposure to 11% oxygen. Specifically, PFF-induced α-syn aggregation resulted in brain tissue hyperoxia, lipid peroxidation and DA neurodegeneration in the SNpc of mice breathing 21% oxygen, but not in those breathing 11% oxygen. This neuroprotective effect of hypoxia was also observed in Caenorhabditis elegans . Moreover, initiating hypoxia 6 weeks after PFF injection reversed motor dysfunction and halted further DA neurodegeneration. These results suggest that hypoxia may have neuroprotective effects downstream of α-syn aggregation in PD, even after symptom onset and neuropathological changes.

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