There is a saying that even amrut (nectar), when taken in excess, can become poison. The same is true of oxygen. At abnormally high levels, oxygen can damage tissues and organs. A new study in Nature Neuroscience reports that in Parkinson’s disease, cellular dysfunction leads to an accumulation of oxygen in the brain, which, in turn, drives neurodegeneration. Interestingly, the potential solution may lie in a low-oxygen environment—similar to the thin air at Mount Everest’s base camp.
Researchers from Harvard Medical School, Massachusetts General Hospital and the Broad Institute of MIT and Harvard found that exposing mice with a Parkinson’s-like condition to reduced oxygen levels helped restore their movement, reduced anxiety-like behaviours and halted further loss of neurons in the brain.
Parkinson’s disease affects more than 10 million people worldwide. It is marked by the progressive loss of neurons in the brain, leading to tremors and slowed movements. These neurons gradually accumulate toxic protein clumps called Lewy bodies, which are believed to disrupt mitochondrial function that powers the cell.
Anecdotal evidence show that people with Parkinson’s often report doing better at high altitudes. Similarly, long-term smokers—who typically have elevated carbon monoxide and lower oxygen levels in their tissues—appear to have a lower risk of developing Parkinson’s, though smoking carries significant risks for many other diseases.
However, researchers caution that the neurological recovery seen in mice has not yet been verified in humans. They also warn that unsupervised exposure to low-oxygen air can be dangerous and may even worsen Parkinson’s disease.
Still, the findings in mice open the door to an entirely new paradigm for treating Parkinson’s. Researchers in the team had previously observed that low oxygen could ease neurological symptoms in rare mitochondrial disorders such as Leigh syndrome and Friedreich’s ataxia.
In the latest study, researchers placed mice in a hypoxic environment after Parkinson’s symptoms had already appeared. As the mice showed a rebound in motor skills and a halt in neuron loss, scientists suggest that early intervention could potentially restore neural function in Parkinson’s patients.
To probe the underlying mechanism, the team analysed mouse brain cells. They found that mice with Parkinson’s symptoms had significantly higher oxygen levels in certain brain regions compared to the healthy mice and those exposed to low oxygen. This excess oxygen likely accumulates because dysfunctional mitochondria are unable to use it efficiently, leading to damaging levels.
Building on these findings, researchers are now developing experimental ‘hypoxia-in-a-pill’, designed to mimic the protective effects of low oxygen. They believe this approach may hold promise for other forms of neurodegeneration, too.