Sleep is one of the most basic, yet most mystifying processes of the human body. It has confounded physicians, scientists and evolutionary biologists for centuries. Scientists have known for a while that an unusual sleep routine or insufficient sleep can lead to mental as well as physical illness. Sleeping disorders are found to be the root cause of many diseases including dementia. The recent research conducted by researchers at the Harvard Medical School has discovered that sleep may be regulated in part by brain-based immune proteins. This study was conducted in mice and led by investigators at Harvard Medical School and VA Boston Healthcare System.
The immune proteins are collectively known as inflammasome NLRP3, said researchers at Harvard Medical School, US. The inflammasome – which works by unleashing a cascade of immune molecules in response to inflammation and infection – emerges as a central promoter of sleep following such events. Scientists have known for a while that certain immune molecules enhance sleep and are activated by infection, but this is the first study suggesting a common underlying mechanism that regulates sleep and plays a critical role in recuperative sleep responses.
Results of the study showed that the inflammasome recruits a sleep-inducing molecule to trigger somnolence following sleep deprivation and exposure to a bacterial toxin. Animals which lack genes for this protective immune complex showed profound sleep aberrations. “Our research points, for the first time, to the inflammasome acting as a universal sensing mechanism that regulates sleep through the release of immune molecules,” said study senior investigator Mark R. Zielinski, instructor in psychiatry at HMS.
The observations suggest that the inflammasome, the constellation of sleep-regulating proteins, may play an evolutionary role as a guardian of brain health and vitality that wards off the effects of sleep deprivation and infection. The investigators compared the behavior, sleep patterns and electrical activity in the brains of mice lacking the inflammasome gene to those in a group of mice with intact inflammasome genes. Mice lacking the inflammasome gene had abnormal sleep responses following sleep deprivation. On average, such mice slept less and experienced more sleep interruptions than mice with their genes intact.
Electrical tracings of sleep activity were also altered in mice lacking the inflammasome NLRP3 gene. These animals lacked the normally seen spikes in delta waves–telltale EEG tracings that indicate sleep intensity, the researchers observed. Additionally, mice lacking the inflammasome NLRP3 gene did not show the normal sleepiness usually seen after exposure to a common sugar-and-fat molecule, a lipopolysaccharide found in the cell walls of some bacteria and known to activate the immune systems of mammals. These animals slept less and less soundly, compared with mice that had intact inflammasome genes. The latter group slept more and harder following bacterial exposure–the expected physiological response following infection, the researchers said.