Breathing CO2 activates brain cleanup signals in new Parkinson’s study
Early findings suggest breathing cycles affect brain clearance systems
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- Brief CO2 breathing activated brain cleanup systems linked to toxic proteins in Parkinson’s disease.
- This approach increased cerebrospinal fluid flow and clearance-related signals in the brain.
- Early findings suggest the method is feasible and well tolerated, supporting future clinical trials.
Breathing carbon dioxide (CO2) for brief periods may help activate the brain’s natural cleanup systems that remove toxic proteins in people with Parkinson’s disease, according to a new study.
Researchers stressed that more work is needed to confirm the results and evaluate the clinical relevance of this approach, but said their study lays the foundation for future trials to determine whether this non-invasive intervention may influence brain cleanup processes involved in Parkinson’s disease.
The study, “The influence of intermittent hypercapnia on cerebrospinal fluid flow and clearance in Parkinson’s disease and healthy older adults,” was published in npj Parkinson’s Disease.
Brain cleanup plays key role in Parkinson’s disease
Parkinson’s disease is a neurological disorder in which certain brain cells become damaged and eventually die. The underlying causes of Parkinson’s aren’t fully understood, but a key feature of the disease is that the protein alpha-synuclein forms abnormal clumps that are toxic to nerve cells. These abnormal alpha-synuclein protein clumps are thought to play a key role in driving the disease, and finding ways to help the brain remove or manage these harmful proteins is a major focus of Parkinson’s research.
Intermittent hypercapnia (breathing in high levels of CO2 for brief periods) can trigger vasomotion — in other words, blood vessels widen and contract in response to changes in carbon dioxide levels in the blood. In the brain, this process can help promote the flow of cerebrospinal fluid (CSF), the fluid that surrounds and supports the brain and spinal cord. This process normally occurs during sleep, but researchers speculated that a similar strategy could be used while a person is awake to increase CSF flow and help carry toxic proteins out of the brain.
“We realized that we may be able to mimic, in the awake state, the [CSF flow] that typically occurs during deep sleep using intermittent CO2,” Sephira Ryman, PhD, study co-author at Touro University, said in a university news story.
Study tests whether breathing CO2 affects brain cleanup activity
To test this idea, the researchers first conducted a proof-of-concept study in which 30 people with Parkinson’s disease underwent intermittent hypercapnia while undergoing MRI scans. This experiment was designed to determine whether intermittent hypercapnia could increase CSF flow through the brain, and the results showed that it did.
The researchers also performed similar tests in 33 older adults without neurological disease. Results in healthy adults also showed that intermittent hypercapnia increased CSF flow, though the effect was markedly stronger in adults without neurological disease than in people with Parkinson’s.
Building on these findings, the researchers conducted further tests in 10 people — five with Parkinson’s and five without — who had blood drawn before and after undergoing a longer intermittent hypercapnia intervention. Data showed that after intermittent hypercapnia, blood levels of alpha-synuclein increased, consistent with activation of brain cleanup processes that help clear proteins from the brain. Several other brain-derived proteins also showed increased blood levels following intermittent hypercapnia, further supporting activation of clearance-related mechanisms.
“Together, this highlights that intermittent hypercapnia can activate key mechanisms involved in … clearance of brain derived proteins … implicated in neurodegeneration,” the scientists wrote.
The researchers also noted that intermittent hypercapnia was generally well tolerated, with no moderate or severe adverse events reported. These findings lay the foundation for future clinical trials to test this approach in Parkinson’s disease, the team said, noting that the study included a small number of participants and only short-term follow-up.
