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Sleep, noradrenaline, and Alzheimer's disease
Lane Simonian
Posted: Sunday, March 5, 2017 9:44 AM
Joined: 12/12/2011
Posts: 5158


Sun's post on sleep and the clearing of toxins in the brain has opened a new line of inquiry. I had read before that sleep helps clear toxins from the brain but what I was missing was the mechanism.  Now it appears we have the mechanism.

A mouse study suggests that sleep helps restore the brain by flushing out toxins that build up during waking hours. The results point to a potential new role for sleep in health and disease.

Scientists and philosophers have long wondered why people sleep and how it affects the brain. Sleep is important for storing memories. It also has a restorative function. Lack of sleep impairs reasoning, problem-solving, and attention to detail, among other effects. However, the mechanisms behind these sleep benefits have been unknown.

Dr. Maiken Nedergaard and her colleagues at the University of Rochester Medical Center recently discovered a system that drains waste products from the brain. Cerebrospinal fluid, a clear liquid surrounding the brain and spinal cord, moves through the brain along a series of channels that surround blood vessels. The system is managed by the brain’s glial cells, and so the researchers called it the glymphatic system.

Changes in the way fluid moves through the brain between conscious and unconscious states may reflect differences in the space available for movement. To test the idea, the team used a method that measures the volume of the space outside brain cells. They found that this “extracellular” volume increased by 60% in the brain’s cortex when the mice were asleep or anesthetized.

The researchers next injected mice with labeled beta-amyloid and measured how long it lasted in their brains when they were asleep and awake. Beta-amyloid disappeared twice as quickly in the brains of mice that were asleep.

Glial cells control flow through the glymphatic system by shrinking and swelling. The hormone noradrenaline, which increases alertness, is known to cause cells to swell. The researchers thus tested whether the hormone might affect the glymphatic system. Treating mice with drugs that block noradrenaline induced a sleep-like state and increased brain fluid flow and extracellular brain volume. This result suggests a molecular connection between the sleep-wake cycle and the brain’s cleaning system.

Noradrenaline which is a product of psychological stress has already been connected to neuropsychiatric problems in Alzheimer's disease, dementia with Lewy bodies, and frontotemporal lobe dementia.  Now it appears to affect the ability of the brain to flush toxins out of the brain by disrupting sleep.  This may explain why high levels of noradrenaline and the subsequent lack of sleep negatively effects episodic memory (the ability to retrieve events) and executive function (including the ability to put things together into "logical" order).

Compounds such as linalool in lavender essential oil via aromatherapy and ferulic acid in Korean red ginseng, rice bran oil, and Angelica archangelica lower noradrenaline levels, improve sleep, and help with various forms of memory.



Lane Simonian
Posted: Sunday, March 5, 2017 9:56 AM
Joined: 12/12/2011
Posts: 5158


The swelling of microglia prevents them from doing their job.  This includes the removal of amyloid plaques, but probably more importantly the removal of toxins.

Dr. Grietje Krabbe of the laboratory of Professor Helmut Kettenmann (MDC) and Dr. Annett Halle of the Neuropathology Department of the Charité headed by Professor Frank Heppner demonstrated that the microglial cells around the deposits do not show the classical activation pattern in mouse models of Alzheimer´s disease. On the contrary, in the course of the Alzheimer’s disease they lose two of their biological functions. Both their ability to remove cell fragments or harmful structures and their directed process motility towards acute lesions are impaired. The impact of the latter loss-of-function needs further investigation. The plaques consist of protein fragments, the beta-amyloid peptides, which in Alzheimer’s disease are deposited in the brain over the course of years...

So in Alzheimer's disease you get all the negative aspects of inflammation with none of the benefits.



Lane Simonian
Posted: Sunday, March 5, 2017 10:29 AM
Joined: 12/12/2011
Posts: 5158


Very simply: oxidative stress by damaging the blood-brain barrier allows toxins into the brain and oxidative stress by damaging microglia prevents the removal of toxins from the brain.