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null Dream discovery: Melatonin’s key role in REM sleep revealed

A significant breakthrough in the understanding of sleep mechanism opens new promise for treating sleep disorders and associated neuropsychiatric conditions.

SOURCE: RI-MUHC
August 7, 2024

Human sleep unfolds in a precise sequence of non-REM (Rapid Eye Movement) and REM stages, each serving distinct physiological functions. REM sleep plays a pivotal role in memory consolidation and emotional regulation, while non-REM sleep supports physical recovery and repair processes. Disruptions in this cycle can impair cognitive function and increase vulnerability to neuropsychiatric diseases.

In a new study published in the Journal of Neuroscience, a team of scientists led by Dr. Gabriella Gobbi at the Research Institute of the McGill University Health Centre (RI-MUHC) and Dr. Stefano Comai at the University of Padua have pinpointed a crucial regulator of REM sleep and discovered the first molecule capable of selectively acting on REM sleep without altering non-REM sleep. This discovery provides a target for the development of new therapies for serious disorders associated with REM sleep dysfunction, such as Parkinson’s disease and Lewy body dementia—which currently lack effective treatments.

Gabriella Gobbi, MD, PhD, co-senior author of the study, Senior Scientist in the Brain Repair and Integrative Neuroscience (BRaIN) Program at the RI-MUHC, Professor of Psychiatry at McGill University and Canada Research Chair in Therapeutics for Mental Health.
Gabriella Gobbi, MD, PhD, co-senior author of the study, Senior Scientist in the Brain Repair and Integrative Neuroscience (BRaIN) Program at the RI-MUHC, Professor of Psychiatry at McGill University and Canada Research Chair in Therapeutics for Mental Health.

Also known as the sleep hormone, melatonin is a molecule secreted by the pineal gland in the brain. It facilitates sleep by acting on receptors involved in the regulation of circadian rhythms and sleep, named MT1 and MT2. However, until now, the specific receptor triggering REM sleep had eluded scientists. The new study has identified the melatonin MT1 receptor as an important regulator of this sleep stage.

“This discovery not only advances our understanding of sleep mechanisms but also holds significant clinical potential,” says Dr. Gobbi, co-senior author of the study, Senior Scientist in the Brain Repair and Integrative Neuroscience (BRaIN) Program at the RI-MUHC, Professor of Psychiatry at McGill University and Canada Research Chair in Therapeutics for Mental Health.

The science of snoozing

In the brain, melatonin’s MT1 receptor interacts with a type of neuron called noradrenaline (or norepinephrine) found in an area known as the locus coeruleus, or “blue spot” in Latin. During REM sleep, these neurons quiet down and stop their activity.

Using a novel drug that activates MT1 receptors, researchers were able to reduce the activity of these neurons in experimental animals, with the effect of successfully increasing the duration of REM sleep. This breakthrough is significant because current sleep-facilitating drugs typically only increase the duration of non-REM sleep.

“Currently, there are no drugs specifically targeting REM sleep. Most hypnotic drugs on the market, while extending total sleep duration, tend to adversely affect REM sleep,” says Dr. Comai, co-senior author of the study, Professor at the University of Padua and Adjunct Professor at McGill University.

Approximately 0.5-1% of the general population is affected by REM sleep behaviour disorder, which is a serious risk factor for the development of certain neurodegenerative diseases. Further research into the neurobiology and pharmacology of REM sleep is crucial for developing targeted treatments that could improve the quality of life for patients affected by these debilitating diseases, according to the researchers. As scientists continue to explore the complexities of sleep regulation, the hope for effective interventions in neurological disorders grows increasingly promising.

About the study

Selective enhancement of REM sleep in male rats through activation of MT1 receptors located in the locus coeruleus norepinephrine neurons by Martha López-Canul, Stefano Comai, Gabriella Gobbi et al., was published in the Journal of Neuroscience on July 17, 2024.

This work was supported by grants from the Canadian Institutes of Health Research, the McGill University Health Centre (MUHC), the Canada Foundation for Innovation and the Canada Research Chairs.