Integrated within us is our own internal body clock, referred to as the circadian clock, that drives our natural sleep and wake cycles and plays a critical role in our physical and mental wellbeing. But, what happens when our body's daily rhythms become disrupted? Long-term deterioration of daily cycles can lead to fatigue, insomnia and memory loss, as seen in “jet lag.” Research has shown that these rhythms’ dysregulation can contribute to various neurological and psychiatric diseases, such as Alzheimer's and Parkinson’s diseases, but the mechanisms are still unknown. 

In a search for answers, Ruifeng (Ray) Cao, MD, PhD, assistant professor in the Department of Biomedical Sciences at the University of Minnesota Medical School, Duluth Campus, and his lab are teaming up with neuroscientists around the country to piece together the puzzles associated with circadian sleep disorders. 

“People with neurodegenerative disorders, such as Alzheimer’s disease, often have disrupted sleep and wake cycles,” Dr. Cao said. “These disruptions often occur much earlier in people whose memories are intact but show some evidence of Alzheimer’s in their brain scans. Patients often experience frequent awakenings at night and wake fragmentation during the day, as patients spend much of the daytime napping.” 

Years of research have demonstrated the mTOR signaling, a fundamental biochemical pathway, is especially important for the brain’s clock function. FDA-approved mTOR inhibitors are known to cause sleep problems. A significant grant from the National Institute of Neurological Disorders and Stroke (NINDS), totaling $1.8 million over five years, will focus on collecting new knowledge critical to understanding the role of mTOR activities in the brain clock that are associated with abnormal behavioral conditions. The research will involve innovative and multidisciplinary approaches to study circadian clock functions at the molecular, cellular and animal behavioral levels, utilizing the latest mouse genetic models to address important questions. 

“There is an increasing list of mTOR-related diseases in which patients show disrupted daily rhythms,” Dr. Cao said. “The biomarkers of the endogenous clock, including melatonin and cortisol levels, are significantly altered in these patients. To understand the abnormal, we have to start by looking at normal conditions. As someone with a PhD and a medical background, I feel driven to do biomedical research that will make a difference in tomorrow’s medicine.”