Sleeping on your side may clear waste from your brain most effectively

The brain’s glymphatic pathway clears harmful wastes, especially during sleep. This lateral position could prove to be the best position for the brain-waste clearance process (credit: Stony Brook University)

Sleeping in the lateral, or side position, as compared to sleeping on one’s back or stomach, may more effectively remove brain waste, and could reduce the chances of developing Alzheimer’s, Parkinson’s and other neurological diseases, according to researchers at Stony Brook University.

Stony Brook University researchers discovered this in experiments with rodents by using dynamic contrast magnetic resonance imaging (MRI) to image the brain’s glymphatic pathway, a complex system that clears wastes and other harmful chemical solutes from the brain. They also used kinetic modeling to quantify the CSF-ISF exchange rates in anesthetized rodents’ brains in lateral, prone, and supine positions.

Colleagues at the University of Rochester used fluorescence microscopy and radioactive tracers to validate the MRI data and to assess the influence of body posture on the clearance of amyloid from the brains.

Their finding is published in the Journal of Neuroscience.

Most popular position in humans and animals

“It is interesting that the lateral sleep position is already the most popular in human and most animals —even in the wild — and it appears that we have adapted the lateral sleep position to most efficiently clear our brain of the metabolic waste products that built up while we are awake,” says Maiken Nedergaard, PhD, a co-author at the University of Rochester.

“The study therefore adds further support to the concept that sleep subserves a distinct biological function of sleep and that is to ‘clean up’ the mess that accumulates while we are awake. Many types of dementia are linked to sleep disturbances, including difficulties in falling asleep. It is increasing acknowledged that these sleep disturbances may accelerate memory loss in Alzheimer’s disease.”

The brain-waste clearing system

Cerebrospinal fluid (CSF) filters through the brain and exchanges with interstitial fluid (ISF) to clear waste in the glymphatic pathway, similar to the way the body’s lymphatic system clears waste from organs. The glymphatic pathway is most efficient during sleep. Brain waste includes amyloid β (amyloid) and tau proteins, chemicals that negatively affect brain processes if they build up.

Helene Benveniste, MD, PhD, Principal Investigator and a Professor in the Departments of Anesthesiology and Radiology at Stony Brook University School of Medicine, cautioned that further testing with MRI or other imaging methods in humans is necessary.

New York University Langone Medical Center was also involved in the research.


Abstract of The Effect of Body Posture on Brain Glymphatic Transport

The glymphatic pathway expedites clearance of waste, including soluble amyloidβ (Aβ) from the brain. Transport through this pathway is controlled by the brain’s arousal level because, during sleep or anesthesia, the brain’s interstitial space volume expands (compared with wakefulness), resulting in faster waste removal. Humans, as well as animals, exhibit different body postures during sleep, which may also affect waste removal. Therefore, not only the level of consciousness, but also body posture, might affect CSF–interstitial fluid (ISF) exchange efficiency. We used dynamic-contrast-enhanced MRI and kinetic modeling to quantify CSF-ISF exchange rates in anesthetized rodents” brains in supine, prone, or lateral positions. To validate the MRI data and to assess specifically the influence of body posture on clearance of Aβ, we used fluorescence microscopy and radioactive tracers, respectively. The analysis showed that glymphatic transport was most efficient in the lateral position compared with the supine or prone positions. In the prone position, in which the rat’s head was in the most upright position (mimicking posture during the awake state), transport was characterized by “retention” of the tracer, slower clearance, and more CSF efflux along larger caliber cervical vessels. The optical imaging and radiotracer studies confirmed that glymphatic transport and Aβ clearance were superior in the lateral and supine positions. We propose that the most popular sleep posture (lateral) has evolved to optimize waste removal during sleep and that posture must be considered in diagnostic imaging procedures developed in the future to assess CSF-ISF transport in humans.

Intracellular microlasers for precise labeling of a trillion individual cells

Massachusetts General Hospital investigators have induced subcutaneous fat cells in a piece of skin from a pig to emit laser light in response to energy delivered through an optical fiber (credit: Matjaž Humar and Seok Hyun Yun/Nature Photonics)

Imagine being able to label a trillion cells in the body to detect what’s going on in each individual cell.

That’s the eventual goal of a Massachusetts General Hospital (MGH) study to allow individual cells to produce laser light. The wavelengths of light emitted by these intracellular microlasers differ based on factors such as the size, shape, and composition of each microlaser, allowing precise labeling of individual cells.

“The fluorescent dyes currently used for research and for medical diagnosis are limited because they emit a very broad spectrum of light,” explains Seok Hyun Yun, PhD, of the Wellman Center for Photomedicine at MGH, corresponding author of the report. “As a result, only a handful of dyes can be used at a time, since their spectral signatures would overlap.”

(Left) Bright-field image of a HeLa cell containing a polystyrene fluorescent bead. (Right) False-color image of the cell. (scale bars: 10 micrometers) (credit: Matjaž Humar and Seok Hyun Yun/Nature Photonics)

Lead author Matjaž Humar, PhD, also of the Wellman Center, adds, “The narrow-band spectrum of light emitted by these intracellular lasers would allow us to label thousands — in principle, up to a trillion — of cells individually [the estimated number of cells in the human body], and the very specific wavelengths emitted by these microlasers also would allow us to measure small changes happening within a cell with much greater sensitivity than is possible with broadband fluorescence.”

The trick is to use solid plastic fluorescent microbeads, which are readily taken up into cells, each with a unique signature spectrum based on the size and number of beads within a cell and the fluorescent dye used.

“One immediate application of these intracellular lasers could be basic studies, such as understanding how cells move and respond to external forces,” says Yun, an associate professor of Dermatology at Harvard Medical School.

“Another challenging step will be figuring out how to use biologically generated energy from mechanical movement or a biochemical reaction to pump a cellular laser in a living body. Cells are smart machines, and we are interested in exploiting their amazing capabilities by developing smart-cell lasers that might be able to find diseases and fire light at them on their own.

“We can envision lasers completely made out of materials that are safe for use within the human body, which could enable remote sensing within the body or be used in laser-light therapies.”

The researchers’ report has received Advance Online Publication in Nature Photonics.


Abstract of Intracellular microlasers

Optical microresonators, which confine light within a small cavity, are widely exploited for various applications ranging from the realization of lasers and nonlinear devices to biochemical and optomechanical sensing. Here we use microresonators and suitable optical gain materials inside biological cells to demonstrate various optical functions in vitro including lasing. We explore two distinct types of microresonator—soft and hard—that support whispering-gallery modes. Soft droplets formed by injecting oil or using natural lipid droplets support intracellular laser action. The laser spectra from oil-droplet microlasers can chart cytoplasmic internal stress (∼500 pN μm–2) and its dynamic fluctuations at a sensitivity of 20 pN μm–2 (20 Pa). In a second form, whispering-gallery modes within phagocytized polystyrene beads of different sizes enable individual tagging of thousands of cells easily and, in principle, a much larger number by multiplexing with different dyes.