A low-oxygen environment - similar to the thin air found at Mount Everest base camp - can protect the brain and restore movement in mice with a Parkinson's-like disease, according to a new study led by scientists at Harvard Medical School, Massachusetts General Hospital, and the Broad Institute of MIT and Harvard.
- By SARAH C. P. WILLIAMS | Broad Institute
The findings, published Aug. 6 in Nature Neuroscience, suggest that cellular dysfunction in Parkinson's disease leads to the accumulation of excess oxygen in the brain, which in turn fuels neurodegeneration.
The results hint that reducing oxygen intake could prevent or even reverse Parkinson's symptoms. However, mice are not humans, and more research is needed to verify whether the same mechanism is at work in people with the disease.
"The fact that we actually saw some reversal of neurological damage is really exciting," said co-senior author Vamsi Mootha, HMS professor of systems biology and medicine at Mass General and an institute member of the Broad Institute.
"The results raise the possibility of an entirely new paradigm for addressing Parkinson's disease," added co-senior author Fumito Ichinose, the HMS William T. G. Morton Professor of Anaesthesia at Mass General.
The researchers caution that it's too soon to translate the results into treatment recommendations for people with Parkinson's - and emphasize that unsupervised breathing of low-oxygen air can be dangerous and may even worsen the disease.
However, they're optimistic that if the findings are eventually confirmed in humans, they could spur the development of new treatment strategies for the disease - for example, drugs that mimic the effects of low oxygen.
A long-standing link explored
Parkinson's disease, which affects more than 10 million people worldwide, causes the progressive loss of neurons in the brain, leading to tremors and slowed movements. Neurons affected by Parkinson's gradually accumulate toxic protein clumps called Lewy bodies, which may interfere with the function of mitochondria - the tiny powerhouses of cells.
Anecdotally, people with Parkinson's seem to fare better at high altitudes. Moreover, long-term smokers - who have elevated levels of carbon monoxide and lower levels of oxygen in their tissues - appear to have a lower risk of developing the disease.
The new study builds on a decade of research from Mootha and others into hypoxia - the condition of having lower than normal oxygen levels in the body or tissues - and its unexpected ability to protect against mitochondrial disorders.
"We first saw that low oxygen could alleviate brain-related symptoms in some rare diseases where mitochondria are affected, such as Leigh syndrome and Friedreich's ataxia," Mootha said.
The findings raised the question of whether the same could be true in Parkinson's.
A new paradigm for Parkinson's
Mootha and Ichinose turned to a well-established mouse model of Parkinson's, in which animals are injected with alpha-synuclein proteins that seed the formation of Lewy bodies.
The mice were split into two groups. One group breathed normal air containing 21 percent oxygen. The other group breathed air with 11 percent oxygen - comparable to living at an altitude of about 16,000 feet.
Three months after receiving the alpha-synuclein protein injections, the mice breathing normal air had high levels of Lewy bodies, many dead neurons, and severe movement problems. The mice breathing low-oxygen air still developed abundant Lewy bodies but didn't lose any neurons and showed no signs of movement problems.
