Individual neurons coordinate to produce rhythmic waves that propel fluid through dense brain tissue, washing the tissue in the process, according to new research from Washington University in St Louis.
The accumulation of metabolic waste is a leading cause of numerous neurological disorders, yet we still have only limited knowledge of how the brain performs self-cleansing. Jiang-Xie et al. demonstrate that neural networks synchronize individual action potentials to create large-amplitude, rhythmic and self-perpetuating ionic waves in the interstitial fluid of the brain. Image credit: Jiang-Xie et al., doi: 10.1038/s41586-024-07108-6.
“These neurons are miniature pumps,” said Dr. Li-Feng Jiang-Xie, first author of the study.
“Synchronized neural activity powers fluid flow and removal of debris from the brain.”
“If we can build on this process, there is the possibility of delaying or even preventing neurological diseases, including Alzheimer’s and Parkinson’s disease, in which excess waste — such as metabolic waste and junk proteins — accumulate in the brain and lead to neurodegeneration.”
Brain cells orchestrate thoughts, feelings and body movements, and form dynamic networks essential for memory formation and problem-solving.
But to perform such energy-demanding tasks, brain cells require fuel. Their consumption of nutrients from the diet creates metabolic waste in the process.
“It is critical that the brain disposes of metabolic waste that can build up and contribute to neurodegenerative diseases,” said Professor Jonathan Kipnis, senior author of the study.
“We knew that sleep is a time when the brain initiates a cleaning process to flush out waste and toxins it accumulates during wakefulness. But we didn’t know how that happens.”
“These findings might be able to point us toward strategies and potential therapies to speed up the removal of damaging waste and to remove it before it can lead to dire consequences.”
But cleaning the dense brain is no simple task. Cerebrospinal fluid surrounding the brain enters and weaves through intricate cellular webs, collecting toxic waste as it travels.
Upon exiting the brain, contaminated fluid must pass through a barrier before spilling into the lymphatic vessels in the dura mater — the outer tissue layer enveloping the brain underneath the skull.
But what powers the movement of fluid into, through and out of the brain?
“Studying the brains of sleeping mice, the researchers found that neurons drive cleaning efforts by firing electrical signals in a coordinated fashion to generate rhythmic waves in the brain,” Dr. Jiang-Xie said.
The study authors determined that such waves propel the fluid movement.
They silenced specific brain regions so that neurons in those regions didn’t create rhythmic waves.
Without these waves, fresh cerebrospinal fluid could not flow through the silenced brain regions and trapped waste couldn’t leave the brain tissue.
“One of the reasons that we sleep is to cleanse the brain,” Professor Kipnis said.
“And if we can enhance this cleansing process, perhaps it’s possible to sleep less and remain healthy.”
“Not everyone has the benefit of eight hours of sleep each night, and loss of sleep has an impact on health.”
“Other studies have shown that mice that are genetically wired to sleep less have healthy brains.”
“Could it be because they clean waste from their brains more efficiently?”
“Could we help people living with insomnia by enhancing their brain’s cleaning abilities so they can get by on less sleep?”
The study was published February 28, 2024 in the journal Nature.
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LF. Jiang-Xie et al. Neuronal dynamics direct cerebrospinal fluid perfusion and brain clearance. Nature, published online February 28, 2024; doi: 10.1038/s41586-024-07108-6
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