MedicalResearch.com Interview with:
Mark Robert Zielinski, MD
Department of Psychiatry
Harvard Medical School and Veterans Affairs Boston Healthcare System
West Roxbury, MA 02132
MedicalResearch.com: What is the background for this study?
Response: Anecdotally, people have known that the immune system and sleep are related. In the last several decades this relationship has been systematically investigated. This work led to important findings that several molecules that enhance inflammation including interleukin-1 beta regulate sleep. Interleukin-1 beta is known to increase sleep and sleep intensity after sleep loss and in response to pathogens. However, it was unknown how these effects are connected. Interestingly, the NLRP3 inflammasome is a protein complex that senses changes in the local environment and subsequently activates pro-inflammatory molecules including interleukin-1 beta. Therefore, we wanted to see if the NLRP3 inflammasome is involved in sleep regulation.
MedicalResearch.com: What are the main findings?
Response: For the first time, we demonstrate the NLRP3 inflammasome is a universal sensing mechanism involved in inducing sleep after sleep loss and pathogen toxin. We found that mice lacking the NLRP3 gene do not exhibit the typical enhanced sleep and sleep intensity responses after either sleep loss or administration of a pathogen toxin. We also found that the molecular machinery of the NLRP3 inflammasome and interleukin-1 beta are enhanced in the brain after sleep loss and at times of the day when sleep propensity is greatest.
MedicalResearch.com: What should readers take away from your report?
Response: Inflammation and sleep are intertwined and tightly regulated processes. Sleep and sleep loss can affect inflammation and vice versa. Therefore, understanding the particular mechanism involved in these processes, such as inflammasomes, are necessary so that effective treatments can be made for individuals with conditions of increased inflammation and dysregulated sleep including sleep apnea, cancer, schizophrenia, and Alzheimer’s disease and veterans who often experience debilitating sleep disturbances.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Based upon our findings, it will be important to investigate the role of inflammasomes in different types of viral and bacterial infections and conditions where people exhibit disturbed sleep.
MedicalResearch.com: Is there anything else you would like to add?
Response: Evidence in the literature suggests that sleep can aid in resolving infection. It is plausible that inflammasomes are involved in this relationship. However, sleep and the immune system are complex and much more research on sleep and immune functions is needed.
The work was supported by the Department of Veterans Affairs Medical Research Service Award 2I01BX001404, Department of Veterans Affairs Medical Research Service Award I01BX002774, and Department of Veterans Affairs Career Award IBX002823A, NIMH-MH016259 fellowship, NINDS-NS079866, NINDS-NS064193, NIMH-MH039683, NHLBI-HL060292 and HL095491, and NIAID-AI118719.
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The NLRP3 inflammasome modulates sleep and NREM sleep delta power induced by spontaneous wakefulness, sleep deprivation and lipopolysaccharide.
Zielinski MR1, Gerashchenko D1, Karpova SA1, Konanki V1, McCarley RW2, Sutterwala FS3, Strecker RE1, Basheer R1.
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