2023-05-01 14:31:31
In mice that sleep too little for a long time, the functioning of special immune cells in the brain, the so-called microglia, is disrupted. As a result, these cells are less able to clear away waste and the protein beta-amyloid clumps together between brain cells, something that also happens in Alzheimer’s disease. That’s according to American research that on Wednesday Science Translational Medicine popped up. Whether this also works in humans remains to be determined.
Inflammatory reactions
The research shows how sleep deprivation affects inflammatory responses and metabolism, and how this is related to beta-amyloid accumulations. And it supports the suspicions that improving sleep or the function of microglia are possible targets for treating that disease.
Persistent sleep deprivation from middle age is associated with a higher risk of dementia later in life, scientists concluded in 2021. For people who slept six hours or less a night in their 50s and 60s, the risk of dementia was 30 percent higher than for people who always slept at least seven hours a night. But at the same time, sleeping problems are also common in people who have dementia. It is not yet clear whether this altered sleep is only a symptom of the disease, or also a cause.
Read also: How sleep deprivation affects your brain
It is known that with a lack of sleep, memory works less well, that inflammatory reactions occur, and that waste products are not flushed away as well. For example, previous studies have shown that after sleep deprivation, higher concentrations of two harmful proteins occur in the cerebrospinal fluid in both mice and humans within a few hours. These are the proteins beta-amyloid and tau, both of which are characteristic of Alzheimer’s disease.
Microglia are crucial for clearing up such protein deposits and other damage. People with a mutation in an important gene in those cells (called TREM2) have an increased risk of Alzheimer’s disease. That mutation prevents microglia from traveling properly to damaged areas in the brain to clear beta-amyloid plaques.
Whether this also applies to humans remains to be investigated
In the latest research, the Americans wanted to unravel exactly what effects chronic sleep deprivation has on those immune cells in the brain. They studied microglia in ordinary lab mice and in modified mice that make beta-amyloid plaques, a model for Alzheimer’s. Half of the mice were kept awake by a moving rod that moved across the entire bottom of their cage every 30 seconds for six hours a day while mice are asleep. This happened for six weeks – in a period roughly comparable in duration to twenty years in humans.
In the brains of mice with sleep deprivation, many more beta-amyloid plaques were formed than in mice that slept well, and therefore many reactive microglia. But the researchers also saw that part of the increased activity of those microglia was independent of the beta-amyloid plaques. The sleep deprivation therefore also has a direct effect on the inflammatory activity of those cells.
All kinds of metabolic processes were also disrupted in the sleepless mice, probably because of the increased amount of energy needed to stay awake longer. And not just the discharge of accumulated proteins door microglia were disrupted. Under the microscope, the researchers saw that sleep deprivation also led to worsened waste processing in nerve cells and microglia.
“This solid study underscores the idea that sleep has a function, and that a lack of it has effects on inflammatory and metabolic processes that may lead to Alzheimer’s,” says Marcel Olde Rikkert, professor of geriatrics at the Radboudumc Alzheimer Center in Nijmegen. “Whether this also applies to humans remains to be investigated. But it is known that various ‘stressors’ in middle age, such as high blood pressure, obesity, and sleep deprivation, increase the risk of cardiovascular disease and dementia later in life.”
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