Increased neuroinflammation and atherosclerosis in sleep fragmented mice

Abstract

There are roughly 70 million Americans who report insufficient sleep due to work responsibilities, sleep apnea, or lifestyle choices. Altered duration and poor sleep quality are associated with an increase in brain inflammation, high rates of cardiovascular disease and other inflammatory diseases in humans. It is known that psychological stress is associated with increased atherogenesis, it is also known that sleep fragmentation (SF) can exacerbate and be induced by SF. However, the exact relationship between SF, neuroinflammation, and atherogenesis is not well known. We found that chronic SF led to increased plaque formation in the aortas HFD fed Apoe−/− mice. SF also resulted in alterations in the immune composition of the bone marrow (BM), blood, aortas, and lymph nodes in the HFD fed Apoe−/− mice. Importantly we detected an increased content of myeloid cells in the blood of SF and HFD fed female Apoe−/− mice. There was an increased percentage of CD68+ macrophages in SF Apoe−/− aortas. Additionally, we detected an increase in CD11b expression and inflammatory markers in the brains of mice that were sleep fragmented when compared to control mice. Our data suggest that SF induces elevated myelopoeisis resulting in monocytosis, neutrophilia, and the altered immune composition of the aortas of atherosclerosis-prone mice, resulting in accelerated atherosclerotic plaque burden.