By Dr. Mark R. Zielinski

The question of why we sleep is perplexing. Decades of research, especially in recent years, is beginning to answer this question. Much evidence shows that sleep is critical for proper memory, mood, performance, fatigue, and health. Inadequate or disturbed sleep can result in accidents, reduced work productivity, stress, difficulty in relationships, and impaired health which impacts individuals, relationships and society in general. Unfortunately, current treatments to aid the many people with sleep problems are short lasting or not effective. Thus, scientific discoveries are being pursued to understand why we sleep so that effective targeted treatments can be developed.

Using new scientific methods and technologies developed over the past several decades, research has identified that sleep is an extremely complex and redundant process. Consequently, this has made the identification of mechanisms that regulate sleep difficult. Notwithstanding, scientific experiments have now found that inflammation is at the core of sleep regulation including normal sleep, the increased need to sleep after sleep loss, and sleep difficulties caused by disease and infection.

Inflammation is often increased or unbalanced in individuals with sleep-related disorders including insomnia, sleep apnea, and restless legs syndrome. Individuals who have diseases that tend to increase inflammation such as cancer, cardiovascular disease, stroke, Type 2 diabetes, schizophrenia, Alzheimer’s disease, and autoimmune disorders have an increased tendency for disturbed sleep. Increased inflammation also occurs in the elderly who have more difficulties with sleep than younger individuals. Furthermore, many of our veterans tend to experience increased incidence of inflammatory related illnesses and debilitating sleep disturbances that exceed that of the general public.

Small proteins called cytokines allow cells including brain cells to communicate with each other and prompt inflammation. Many pro-inflammatory cytokines regulate sleep, health, and physiological functions such as cognition, mood, performance, and fatigue that are affected by sleep loss and disease. These pro-inflammatory cytokines are enhanced in the brain with sleep loss and are elevated in the brain at times of the day when one sleeps more. However, the exact mechanisms that regulate these inflammatory-sleep altering molecules have been elusive.

Inflammasomes are protein complexes that form in cells including in brain cells after sensing changes around the cells and produce pro-inflammatory cytokines. We recently discovered that a inflammasomes are an key mechanism regulating sleep. Our work found that inflammasomes are critical to regulating not only normal sleep but sleep occurring after sleep loss and a bacterial toxin. These are extremely exciting finding because inflammasomes appear to be a universal regulator of sleep from both increased brain activity and pathogens.

It is also important to note that not all inflammation is bad and inflammation is vital for many normal body functions and responses to infection — i.e., too much inflammation or not having the proper inflammatory response during the time that the body requires it can be problematic. Inflammasomes themselves are quite complex and it will take time and more research to completely understand their role in health and functioning. However, sleep research is on the cusp of unraveling the mechanisms behind sleep and inflammation and inflammasomes appear to be fundamental.

Dr. Mark R. Zielinski is a Research Health Scientist at VA Boston Healthcare System and an Assistant Professor at Harvard Medical School, Department of Psychiatry. Work described was, in part, conducted with co-investigators Drs. Dmitry Gerashchenko, Svetlana A. Karpova, Varun Konanki, Robert W. McCarley, Fayyaz S. Sutterwala, Robert E. Strecker and Radhika Basheer.

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