Scientists have long recognized the brain鈥檚 need for energy, but groundbreaking research from the University of Kentucky鈥檚 Sanders-Brown Center on Aging has now illuminated how the brain鈥檚 energy utilization significantly influences our sleep patterns.
The study was . It discovered certain channels in the brain, called ATP-sensitive potassium (KATP) channels, act as energy sensors and play a pivotal role in maintaining stable sleep-wake cycles and facilitating smooth transitions between cycles.
The research was led by Nicholas Constantino, a doctoral neuroscience student working in the lab of Shannon Macauley, PhD The project was an interdepartmental collaboration between physiology, neuroscience, Sanders-Brown and the Central Nervous System-Metabolism Centers of Biomedical Research Excellence (CNS-Met COBRE).
This research was supported by multiple awards from the National Institutes of Health鈥檚 National Institute on Aging, National Institute of Neurological Disorders and Stroke, and National Institute of General Medical Sciences. It also received funding from the BrightFocus Foundation and the Alzheimer鈥檚 Association.
The study delved into the impact of metabolic changes on sleep, particularly the molecular mechanisms connecting metabolism and brain cell excitability, using mouse models lacking KATP channels and advanced techniques like EEG monitoring.
鈥淥ur study shows that even small changes in energy usage can profoundly impact behavior,鈥 said Macauley, who is an associate professor of physiology in the 好色先生 College of Medicine.
These changes impact when we sleep, how we sleep and the overall quality of our sleep. The study identified a previously unknown function of KATP channels in sleep regulation.
鈥淲e discovered that KATP channels 鈥 key regulators linking metabolism and excitability 鈥 play a previously unrecognized role in sleep regulation," said Macauley. "We did not fully appreciate the profound role that fuel utilization has on the integrity of sleep and behaviors while we are awake.鈥
The researchers also discovered that KATP channels on neurons have a daily rhythm.
鈥淲e did not know that KATP channels on neurons display a circadian rhythm of expression that suggests a role in regulating sleep," Macauley said. "Additionally, we discovered that KATP channels regulate lactate levels, a key metabolite for transitioning between sleep and wakefulness.鈥
When these channels don鈥檛 function properly, brain cells can鈥檛 tell how much energy they need.
鈥淲hen cells lack the ability to assess their own metabolic needs, essential processes like neurotransmitter synthesis become compromised, which in our study was linked to impaired cognition and increased anxiety,鈥 said Macauley. 鈥淢ost importantly, we found that KATP channels have a profound impact on sleep, particularly in enabling smooth transitions between wakefulness, restorative slow-wave sleep and REM sleep. This is particularly relevant for diseases like Alzheimer鈥檚, diabetes and epilepsy, which are associated with both altered KATP-channel activity and sleep disturbances."
Food and Drug Administration-approved drugs targeting KATP channels already exist, so this research suggests a promising new therapeutic approach for restoring sleep in individuals with Alzheimer鈥檚, epilepsy or diabetes.
The core message of this research, as stated by the scientists, is the significant impact of fuel sensing and utilization on our sleep and wakefulness.
鈥淎ltering the way the body can sense and use fuel can deeply impact the way we sleep and our behaviors while we are awake,鈥 said Macauley.