Research, REM sleep switch discovered and first targeted drug

New developments on the horizon against sleep disorders and some related neurological diseases. A joint study by the universities of Padua, McGill and Toronto (Canada), published in the ‘Journal of Neuroscience’, has identified the ‘switch’ of REM sleep – the melatonin receptor MT1 – and the first targeted drug, capable of acting selectively on this crucial phase of rest, without altering non-REM sleep. “The clinical potential of the discovery is significant”, they underline from the University of Padua, not only for the understanding of the mechanisms of sleep and therefore for the treatment of its alterations, but above all for those suffering from pathologies such as Parkinson’s and dementia with Lewy bodies.

Human sleep – recalls UniPd – is made up of a precise sequence of non-REM and REM phases, each of which carries out distinct physiological functions. REM sleep (an acronym for Rapid Eye Movement, the rapid eye movement that characterizes it), the one in which we dream, plays a fundamental role in the consolidation of memory and in the regulation of emotions. Non-REM sleep instead supports the processes of recovery and physical repair. Interruptions in this cycle can compromise cognitive functions and increase vulnerability to neuropsychiatric diseases. The authors of the new publication – the result of research on melatonin and its two receptors, MT1 and MT2, developed over the last 15 years by the international team – have identified the MT1 receptor as the key regulator of REM sleep, which has allowed them to identify the first molecule specifically targeted to this sleep phase.

MT1 is expressed in specific neurons called noradrenaline neurons, located in an area of ​​the brain called the Locus Coeruleus (blue dot) because of its bluish color, caused by the melanin granules within it. During REM sleep, these noradrenergic neurons reduce their electrical activity and become silent. Approximately 0.5-1% of the general population suffers from REM sleep behavior disorder, which is a serious risk factor for the development of neurodegenerative diseases such as Parkinson’s disease and other diseases such as dementia with Lewy bodies, for which there are currently no effective treatments. Using a new drug that acts selectively on MT1 receptors, scientists have been able to increase the duration of REM sleep in experimental animals, while simultaneously reducing the activity of noradrenergic neurons in the Locus Coeruleus.

“This discovery not only advances our understanding of sleep mechanisms, but also has significant clinical potential,” says Gabriella Gobbi, principal investigator of the study, professor of Psychiatry at McGill University, clinician at McGill University Health Center, and Canada Research Chair in Therapeutics for Mental Health. “Until now,” she says, “the specific receptor that triggers REM sleep had eluded scientists,” while “the new study has identified the MT1 melatonin receptor located in the Locus Coeruleus as an important regulator of this sleep phase.”

Not only that. “Until now – remarks Stefano Comai, senior co-author of the work, professor of Pharmacology at the University of Padua and adjunct professor at McGill University – there were no drugs specifically aimed at modifying REM sleep. Most of the hypnotic drugs on the market, while prolonging the total duration of sleep, tend to negatively influence REM sleep. With the published study, in addition to revealing the specificity of the MT1 melatonin receptor, we have discovered the first molecule capable of acting selectively on REM sleep without altering non-REM sleep”.

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According to the authors, “further research on the neurobiology and pharmacology of REM sleep is essential to develop targeted treatments that could improve the quality of life of patients with these debilitating neurodegenerative diseases. As scientists continue to explore the complexities of sleep regulation, the hope of effective interventions in neurological disorders becomes increasingly promising.” For the researchers, “if future studies confirm the specific involvement of the melatonin receptor MT1 in the regulation of REM sleep, new drugs could be developed to treat REM sleep disorders, which, as mentioned, are known to be closely linked to, for example, Parkinson’s disease and other related conditions called parkinsonisms, such as dementia with Lewy bodies.”