Improving sleep quality in neurodegeneration

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A new publication in the Journal of Neuroscience, by Mount Sinai researchers, discusses a study conducted by researchers at Mount Sinai, which identifies a new form of treatment for rapid eye movement (REM) sleep behavior disorder. enter image description here This condition affects individuals, mostly adults over the age of 50, who physically act out their dreams during sleep, resulting in injuries to themselves or their bed partners. It's also suspected to be involved in premisses of Parkinson's disease. The study, published in the Journal of Neuroscience, presents a novel model that characterizes how REM sleep behavior disorder develops due to neurodegeneration associated with the accumulation of tau protein.

Tauopathies are a group of neurodegenerative disorders characterized by the abnormal accumulation of tau protein in the brain. DORAs have shown promise in preclinical studies as potential treatments for tauopathies, including diseases like progressive supranuclear palsy (PSP) and frontotemporal dementia with tau pathology.

DORAs have been found to modulate the activity of the orexin system, which is involved in regulating tau pathology. By targeting the orexin system, DORAs may potentially influence tau-related neurodegeneration and associated symptoms. However, further research is needed to fully understand the mechanisms and clinical implications of DORAs in tauopathies.

Using a mouse model, the researchers examined the effects of abnormal tau deposits on brain function and sleep. They analyzed various sleep-related factors, including wakefulness, REM sleep, non-REM sleep, sleep duration, and transitions between sleep stages. The study found that a significant number of older mice exhibited dream enactment behaviors similar to REM sleep behavior disorder, such as chewing and limb extension.

The researchers then administered a type of sleep medication called dual orexin receptor antagonists (DORAs) to evaluate their effects on sleep in the mice. They discovered that the medication not only improved sleep quality and duration but also significantly reduced dream enactment behaviors.

Orexin receptor antagonists (ORAs) are a class of medications that target the orexin system in the brain. Orexins, are neuropeptides that play a crucial role in regulating wakefulness and arousal. They promote wakefulness by activating orexin receptors in cells of the brain.

When orexin receptors are blocked or antagonized by medications, such as dual orexin receptor antagonists (DORAs), it leads to a decrease in wakefulness and an increase in sleepiness. DORAs are primarily used to treat insomnia, as they promote sleep initiation and maintenance.

In terms of sleep architecture, orexin receptor antagonists have been found to affect different sleep stages and sleep characteristics. Here are some of the effects observed:

  • Increased total sleep time, allowing individuals to obtain a longer and more restful sleep.

  • Increased non-rapid eye movement (NREM) sleep), which is deep and restorative sleep, and lighter stages of NREM sleep.

  • Decreased rapid eye movement (REM) sleep: DORAs have been found to suppress REM sleep, the stage associated with vivid dreaming and increased brain activity. This reduction in REM sleep may be beneficial in certain sleep disorders, such as REM sleep behavior disorder.

  • Improved sleep continuity: DORAs can enhance sleep continuity by reducing the number of awakenings during the night and decreasing the time spent awake after sleep onset. This leads to more consolidated and uninterrupted sleep.

It's important to note that the effects of orexin receptor antagonists on sleep architecture may vary depending on the specific medication, dosage, and individual factors.

These findings suggest that DORAs, which are already FDA-approved for treating insomnia, could serve as a promising new treatment for REM sleep behavior disorder. The researchers hope that their study will encourage further clinical trials of DORAs in humans with this disorder.

Overall, the study provides insights into the effects of neurodegeneration and tau protein accumulation on sleep and offers a potential therapeutic approach for managing REM sleep behavior disorder.

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