Prolonged sleep fragmentation of mice exacerbates febrile responses to lipopolysaccharide

• The method used is effective in fragmenting sleep of mice for prolonged periods without behavioral adaptation.
• Although NREM sleep is disrupted and REM sleep is abolished by this method, there is no compensatory increase in sleep during periods without fragmentation.
• Water intake and body weight are unchanged by this protocol, and corticosterone is only modestly elevated.
• After prolonged sleep fragmentation, febrile responses to immune challenge are exacerbated.

BackgroundSleep disruption is a frequent occurrence in modern society. Whereas many studies have focused on the consequences of total sleep deprivation, few have investigated the condition of sleep disruption.New methodWe disrupted sleep of mice during the light period for 9 consecutive days using an intermittently rotating disc.ResultsElectroencephalogram (EEG) data demonstrated that non-rapid eye movement (NREM) sleep was severely fragmented and REM sleep was essentially abolished during the 12 h light period. During the dark period, when sleep was not disrupted, neither NREM sleep nor REM sleep times differed from control values. Analysis of the EEG revealed a trend for increased power in the peak frequency of the NREM EEG spectra during the dark period. The fragmentation protocol was not overly stressful as body weights and water consumption remained unchanged, and plasma corticosterone did not differ between mice subjected to 3 or 9 days of sleep disruption and home cage controls. However, mice subjected to 9 days of sleep disruption by this method responded to lipopolysaccharide with an exacerbated febrile response.Comparison with existing methodsExisting methods to disrupt sleep of laboratory rodents often subject the animal to excessive locomotion, vibration, or sudden movements. This method does not suffer from any of these confounds.ConclusionsThis study demonstrates that prolonged sleep disruption of mice exacerbates febrile responses to lipopolysaccharide. This device provides a method to determine mechanisms by which chronic insufficient sleep contributes to the etiology of many pathologies, particularly those with an inflammatory component.