Summary: A potential new treatment for rapid eye movement (REM) sleep behavior disorder has been identified.
The study established a new model detailing disease progression due to neurodegeneration linked to tau accumulation. Researchers have found that dual orexin receptor antagonists, commonly used for insomnia, significantly reduce the symptoms of this disorder.
The discovery introduces a new treatment option that could potentially have fewer side effects.
Highlights:
- Mount Sinai researchers have discovered a potential new treatment for REM sleep behavior disorder, which affects more than 3 million Americans and involves realizing dreams during sleep.
- The study presented a new model showing how the disorder develops due to neurodegeneration linked to an accumulation of tau protein.
- Sleep medications known as dual orexin receptor antagonists, typically used for insomnia, have been shown to significantly reduce the disorder, opening up a promising new treatment option.
Source: Mount Sinai Hospital
Mount Sinai researchers have published what they say is the first study to identify a new form of treatment for rapid eye movement (REM) sleep behavior disorder.
This condition affects more than 3 million Americans, mostly adults over the age of 50, who often unknowingly physically fulfill their dreams with vocal sounds or sudden violent movements of the arms and legs during sleep, resulting in serious injury to themselves or their bed partners.
The new study, published in the Journal of Neurosciencedescribes a new model to better characterize how REM sleep behavior disorder develops due to neurodegeneration – when brain cells lose function over time – which is associated with the accumulation of tau protein.
This model provides an early biomarker of impending brain damage, which could guide future prevention and treatment.
The article also demonstrates for the first time that sleep medications known as dual orexin receptor antagonists – commonly used to treat insomnia or difficulty falling asleep and staying asleep – can significantly reduce REM sleep behavior disorder.
Current treatment options for this disorder are mostly limited to melatonin and clonazepam, also known as Klonopin, so these results suggest a promising new treatment with potentially fewer side effects.
“We wanted to understand all of the ways in which sleep quality breaks down as neurodegeneration progresses and if there were ways to mitigate these changes,” said corresponding author Andrew W. Varga, MD, Ph.D. ., associate professor of medicine. (pulmonology, critical care, and sleep medicine) at the Icahn School of Medicine at Mount Sinai.
“We identify a novel model in which REM sleep behavior disorder may develop, due to neurodegeneration associated with tau accumulation, and a novel therapy that may minimize REM sleep behavior disorder.”
The Mount Sinai researchers used a mouse model to study neurodegenerative disorders by examining the brain for abnormal deposits of tau, a protein that normally helps stabilize the inner skeleton of nerve cells in the brain.
They analyzed behavioral states including wakefulness, REM (sleep with dreams) stages, non-REM (dreamless sleep) stages, sleep duration, wake-to-sleep transitions, and how some of which are related to age.
Almost a third of the older subjects exhibited dream-acting behaviors reminiscent of REM sleep behavior disorder, including chewing and limb extension.
After administering a dual orexin receptor antagonist twice over a 24-hour period, to assess sleep in the light and dark phases, the researchers observed that the drug not only reduced the time to fall asleep and increased both quality and duration of sleep, but also reduced levels of dream fulfillment.
The researchers hope their findings will encourage future trials of dual orexin receptor antagonists to treat REM sleep behavior disorder in humans, given that the drug is already FDA-approved and available to treat sufferers. insomnia.
“We had anticipated the finding of impaired sleep quality with progressive neurodegeneration linked to tau accumulation, but the observation of dream fulfillment came as a surprise,” said lead author Korey Kam. , Ph.D., assistant professor of medicine (pulmonology, critical care, and sleep medicine) at Icahn Mount Sinai.
“It was even more surprising and exciting to observe that a dual orexin receptor antagonist could significantly minimize dream-acting behaviors.”
About this sleep research news
Author: Andrew W. Varga
Source: Mount Sinai Hospital
Contact: Andrew W. Varga – Mount Sinai Hospital
Picture: Image is credited to Neuroscience News
Original research: Access closed.
“Effect of Aging and a Dual Orexin Receptor Antagonist on Sleep Architecture and NREM Oscillations, Including an REM Behavior Disturbance Phenotype in the PS19 Mouse Model of Tauopathy” by Andrew W. Varga et al. Journal of Neuroscience
Abstract
Effect of aging and a dual orexin receptor antagonist on sleep architecture and NREM oscillations, including an REM behavior disorder phenotype in the PS19 mouse model of tauopathy
The impact of tau pathology on features of sleep microarchitecture, including slow oscillations, spindles, and their coupling, has been understudied, despite the proposed importance of these electrophysiological features for learning and memory. . Dual orexin receptor antagonists (DORAs) are known to promote sleep, but whether and how they affect sleep microarchitecture in tauopathy is unknown.
In the PS19 mouse model of tauopathy (MAPT P301S, male and female), 2–3-month-old young PS19 mice exhibit an electrophysiological signature of sleep with markedly reduced spindle duration and power, and slow oscillation density ( SO) elevated relative to littermate controls, even though there is no significant tau hyperphosphorylation, tangle formation, or neurodegeneration at this age.
With aging, there is evidence of sleep disruption in PS19 mice, characterized by reduced REM duration, increased non-REM and REM fragmentation, and more frequent brief arousals at the macro level, and reduced spindle density, a SO density and a spindle-SO coupling at the micro level. In approximately 33% of aged PS19 mice, we unexpectedly observed abnormal goal-directed behaviors in REM, including chewing, paw grasping, and forelimb/hindlimb extension, apparently consistent with the disorder. REM behavior (RBD).
Oral administration of DORA-12 to aged PS19 mice increased non-REM and REM duration, albeit with shorter episode durations, and increased spindle density, spindle duration, and density SO without modification of the spindle-SO coupling, power in the SO or the spindle bands, or the excitation index.
We observed a significant effect of DORA-12 on objective measures of RBD, thus encouraging future exploration of the effects of DORA on sleep-mediated cognition and RBD processing.