Click the link below the picture
.
When you fall asleep, your brain doesn’t just switch off. As the cognitive lights go out, housekeeping begins. Along the outer walls of blood vessels, microscopic currents flow, sweeping away waste that would otherwise cause harm.
This is the glymphatic system, a network of channels that helps the brain clear unwanted proteins and by-products of cellular metabolism. It may explain one of life’s most familiar pleasures: feeling refreshed after a good night’s sleep. Yet we only learned of its existence in 2012, and ever since, researchers have been scrambling to figure out exactly how it works.
Now, it seems this overlooked system may be crucial for our health – when clearance falters, it may contribute to Alzheimer’s and Parkinson’s disease, and possibly other hard-to-treat conditions, including migraine.
Doctors are eager to intervene, wondering whether boosting this nocturnal detox could slow or even prevent disease. “The field is filled with promise, and we’re just starting to do the studies that will find out if it’s going to make good on that promise,” says neuroscientist Jeffrey Iliff at the University of Washington in Seattle. Experiments range from using drugs and red-light therapy to inhaling bursts of carbon dioxide. There’s also talk of improving brain clearance by changing how we exercise or breathe, or even the position in which we sleep. Meanwhile, emerging techniques hint that we might already be able to gauge the health of our glymphatic system using a simple smartwatch.
Yet the young field has already been dogged by disputed methods, exaggerated headlines and the apparent detention of a key researcher. With so much at stake, it is vital to separate promise from hype, establishing what we can reliably measure, which interventions help clear the waste and whether doing so improves our health and prevents disease.
All our cells produce unwanted chemicals that become harmful if they build up. Luckily, we have an elaborate network of tubes called the lymphatic system that runs throughout the body, collecting fluid from cells, filtering it and sending it to the blood, with waste being expelled by the liver and kidneys.
The strange thing is that there are no lymph vessels in the brain. The implication was that the brain’s waste molecules left passively, drifting through the extracellular fluid surrounding brain cells. But this never made much sense for such an energy-hungry – and therefore heavily waste-creating – organ.
A breakthrough came in 2012, when Iliff and his colleagues injected a fluorescent tracer into the brains of living mice. They targeted the subarachnoid space, a thin region between two of the membranes, or meninges, that encase the brain and spinal cord. The tracers rapidly moved from this space into the brain itself. But they didn’t travel through tubes to do so. Instead, they moved along the outside of small arteries, later leaving the brain along the outer layers of small veins. The brain, it turned out, had a waste-disposal system after all – but it was unlike anything we had seen before.
Closer inspection showed that brain cells called astrocytes, which have long, branch-like projections called endfeet, were wrapped around the blood vessels. The tracer chemicals were moving in the narrow space between the astrocyte endfeet and the outer walls of the blood vessels.
Astrocytes belong to a larger group of brain cells called glial cells, inspiring the name glial lymphatic system, or glymphatic system for short.
Three years later, two groups discovered lymph vessels hidden in the meninges. Another part of the puzzle fell into place: the glymphatic system moves waste out of brain tissue, while the newly discovered lymph vessels take it away from there.
Mapping the glymphatic system was only the start, though: researchers also wanted to know what governs its flow. One vital clue came from the activity that occupies a third of our lives.
Why sleep is key to cleaning the brain
In 2013, Maiken Nedergaard at the University of Rochester in New York state and her team, which included Iliff, injected a green tracer into the cerebrospinal fluid of sleeping mice and watched it stream around the brain. After the mice were gently woken, this flow fell by about 95 per cent. The researchers also showed that beta-amyloid, a key waste product associated with Alzheimer’s disease, was cleared roughly twice as fast when the mice were asleep.
Then last year, Natalie Hauglund, a sleep scientist now at the University of Oxford, and her colleagues helped identify a control mechanism. Studying mice, they showed that concentrations of the neurotransmitter noradrenaline rose and fell about every 50 seconds during non-REM sleep. This caused arteries in the brain to alternately swell and constrict, gently pumping the fluid along the outside.
That mechanism could be key to why glymphatic function declines with age. “As you get older, your arteries become stiffer,” says Roslyn Bill at Aston University in Birmingham, UK. “So, I think that whole mechanism probably breaks down.”
Crucially, Geir Ringstad and Per Kristian Eide at the University of Oslo in Norway demonstrated that the glymphatic system also operates similarly in the human brain and that just one night without sleep is enough to reduce the removal of a tracer from people’s brains.
This was one of the first hints that the glymphatic system can go wrong overnight, but what happens when the brain’s housekeeping falters over months or years?
The strongest links between a faulty glymphatic system and disease concern Alzheimer’s. In people with this form of dementia, beta-amyloid accumulates into distinctive plaques, while abnormal tangles of another protein called tau form inside brain cells.
In 2016, researchers including Nedergaard found there was reduced glymphatic transport in mouse models of Alzheimer’s even before amyloid plaques formed. The implication was that impaired glymphatic clearance might allow beta-amyloid to accumulate in the brain, contributing to disease. Since then, evidence has grown that the glymphatic system transports these proteins in people too – this January, Iliff and his colleagues reported that it helps clear beta-amyloid and tau from the brains of people without dementia.
.
Chris Gash
.
.
Click the link below for the complete article:
.
__________________________________________
Leave a comment