24 Feb Anesthesia Drug and Deep Sleep Use Same Neural Circuits In Brain

MedicalResearch.com Interview
Professor Nick Franks 
Professor of Biophysics and Anaesthetics

Professor William Wisden,
Chair in Molecular Neuroscience
Department of Life sciences
Wolfson Laboratories, Imperial College, South Kensington London

Medical Research: What is the background for this study? What are the main findings?

Profs. Franks and Wisden: We were interested in finding out how a particular type of sedative drug, dexmedetomidine, works in the brain. This drug is increasingly used during intensive care for sedation of patients, but unlike other powerful sedatives, it induces a state whereby the patient can be temporarily woken up. This is a highly useful property because it means patients can be both sedated and responsive during procedures. The drugged sedative state induced by dexmedetomidine struck us as being highly similar to the deep sleep that we all need to have if we have been extensively sleep deprived. If people and animals are kept awake for extended periods of time, they have to sleep. Most people know this from common experience – catching up on lost sleep. But how and why we need to sleep after sleep deprivation is not known. We found that dexmedetomidine-induced sedation and this recovery sleep used the same brain circuits, in a tiny area at the base of the brain called the preoptic hypothalamus. To do this we used a new genetic technique in mice that allowed us to mark or “tag” which neurons in the mouse’s brain were active during sedation or recovery sleep after sleep deprivation. The beauty of this technique is that we could then specifically reactivate these same neurons several days later with a special molecule that only binds to the tagged neurons. This reactivation caused the mice to go into a deep sleep. We concluded that the sedative drug dexmedetomidine copies or hijacks the mechanism used by the brain to respond to sleep deprivation and trigger deep sleep.

Medical Research: What should clinicians and patients take away from your report?

Profs. Franks and Wisden:  Putting patients to sleep during medical procedures is a comforting metaphor and, in the case of dexmedetomidine, at least, this metaphor may be closer to the truth than we had previously thought. The sleep it produces is much deeper that the daily sleep we all experience, and is similar to the profound sleep that follows sleep deprivation.

Medical Research: What recommendations do you have for future research as a result of this study?

Profs. Franks and Wisden: Dexmedetomidine works not only on the brain but also on tissues in the rest of the body, such as heart and blood vessels, where it slows heart rate and reduces blood pressure by dilating arteries. It would be desirable to remove these extra complications, and have a drug that has the neurological effects of dexmedetomidine (strong sleep induction) without the peripheral complications. So our future research will concentrate on understanding what dexmedetomidine’s action in the hypothalamus has in common with the changes signaled by sleep deprivation. We want to understand more about these hypothalamic neurons, what activates them and where they project to in the brain to induce the behavioral effects of sleep and sedation. Elucidating the circuitry and mechanisms involved may lead to both a greater understanding of the natural sleep process, and a cleaner drug that could be the ideal sedative, because it mimics the brain’s sleep homeostat.

Citation:

Zhe Zhang, Valentina Ferretti, İlke Güntan, Alessandro Moro, Eleonora A Steinberg, Zhiwen Ye, Anna Y Zecharia, Xiao Yu, Alexei L Vyssotski, Stephen G Brickley, Raquel Yustos, Zoe E Pillidge, Edward C Harding, William Wisden, Nicholas P Franks. Neuronal ensembles sufficient for recovery sleep and the sedative actions of α2 adrenergic agonists. Nature Neuroscience, 2015; DOI: 10.1038/nn.3957

MedicalResearch.com Interview, Nick Franks FSB, FRCA, FMedSci, FRS, Professor of Biophysics and Anaesthetics, & Professor William Wisden (2015). Anesthesia Drug and Deep Sleep Use Same Neural Circuits In Brain 

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Last Updated on February 25, 2015 by Marie Benz MD FAAD