The microglial response in a rat model of chronic sleep restriction

Chronic sleep restriction (CSR) is prevalent in today’s 24/7 society and has profound consequences on health and cognition. Recent evidence indicates increased levels of inflammatory molecules following CSR; however, the role of microglia, the resident immune cells of the brain, is unknown. Using a rat model of CSR (4 days) that we developed in our lab, we previously found that CSR initiated an increase in the number and density of ionized calcium binding adaptor molecule-1 (Iba1)-immunoreactive (ir) microglia in brain regions involved in sleep/wake and cognitive functions; microglia morphology was unaffected. Here, we explored the mechanisms underlying the region-specific increases in microglia numbers after CSR. First, proliferating cells were immunohistochemically identified using bromodeoxyuridine (BrdU). We found that the number of double-labeled Iba1/BrdU-ir cells was not affected by CSR. Second, blood brain barrier permeability, assessed by examining extravasation of the fluorescent tracers sodium fluorescein and Evans blue into the brain tissue, was also unaffected by CSR. These results suggest that neither microglia proliferation nor the recruitment of peripheral macrophages across the blood-brain barrier contributed to the observed increase in Iba1-ir microglia after CSR, suggesting that increased Iba1 expression may be responsible for the effect. Preliminary results with qPCR indicate decreased mRNA expression (∼60%) of the pro-inflammatory interleukin-1 β and tumor necrosis factor- α and increased expression (∼25%) of the anti-inflammatory IL-10 in the hippocampus after CSR.