“The fact that we actually saw some reversal of neurological damage is really exciting. It tells us that there is a window during which some neurons are dysfunctional but not yet dead — and that we can restore their function if we intervene early enough,” said co-senior author Vamsi Mootha, professor of systems biology and medicine at Harvard Medical School, in a press release.
Anecdotal reports suggest that people with Parkinson's disease experience improved symptoms at higher altitudes. Research also shows that long-term, heavy smoking, which elevates carbon monoxide levels and reduces oxygen in tissues, is protective against Parkinson’s disease. With this in mind, the researchers behind the current study investigated the effects of hypoxia on Parkinson’s disease.
To do so, they injected mice with clumps of the α-synuclein protein to seed the formation of Lewy bodies- abnormal aggregations of protein that develop in neurons affected by Parkinson’s disease. They then exposed the mice to either normal air- 21% oxygen- or air comparable to that at an altitude of 16,000 feet or 4,800 meters- 11% oxygen.
Three months later, the researchers found that mice breathing normal air had high levels of Lewy bodies, dead neurons, and severe movement problems. Those kept in low-oxygen environments, however, didn’t lose any neurons and showed no signs of movement problems even though they also developed abundant Lewy bodies.
The researchers further found that exposure to hypoxia six weeks after the injection- when symptoms were already developing- had neuroprotective effects. It reversed motor dysfunction, reduced anxiety-like behaviors, and stopped further loss of neurons.
The researchers analyzed the brain cells of mice to understand the mechanisms behind the findings. In doing so, they found that mice with Parkinson’s symptoms had significantly higher levels of oxygen in some areas of the brain than controls and those kept in conditions with low-oxygen air. Excess oxygen, they noted, likely stems from mitochondrial dysfunction; damaged mitochondria can’t use oxygen in an efficient way, leading to excessive buildup.
The researchers note that more work is needed before the findings can be used to treat Parkinson’s. Nevertheless, they are currently developing ‘hypoxia in a pill’ drugs to mimic the effects of low oxygen environments to treat mitochondrial disorders.
“It may not be a treatment for all types of neurodegeneration, but it’s a powerful concept — one that might shift how we think about treating some of these diseases,” said Mootha.
Sources: EurekAlert, Nature Neuroscience