Effects And Mechanism Of Sleep Fragmentation On Wakefulness

Study Objectives: To test the long-term effectiveness of a sleep fragmentationapparatus for mice and to determine whether long-term sleep fragmentation haslasting effects on sleep and/or wakefulness.Design: Adult male mice were implanted for sleep state recordings and thenrandomly assigned to4-5weeks of either orbital platform sleep fragmentation (30events/hr) or control conditions followed by a recovery period.Measurements: Arousal frequency, behavioral state transitions, sleep bout length,wake, NREM sleep and REM sleep times, mean sleep latency and state-specificelectroencephalographic spectral analysis measures were obtained at baseline, withinweeks1and5of sleep fragmentation or control condition, and again after2wksrecovery.Results: Orbital movement of the cage increased the frequency of behavioral statetransitions and arousals throughout five weeks. Across sleep fragmentation,progressive changes in the electroencephalographic power spectra were observedincluding increased delta power in wakefulness and NREM sleep. An absence of deltapower decline developed across the lights-on period. Total sleep/wake times wereunchanged. Fragmentation of sleep and wake resolved after2wks recovery time;however, waking electroencephalographic power remained shifted to slowerfrequencies, and total wake time during the lights-on period was reduced.Conclusions: Orbital rotor movement is an effective means of long-term sleepfragmentation.Chronic sleep fragmentation imparts significant changes in sleepconsolidation, sleep latency and spectral power of the electroencephalogram for allbehavioral states. Study Objectives:To test the long-term effectiveness of sleep fragmentation on sleepand/or wakefulness, to test the hypothesis that sleep fragmentation could result inimpaired arousal responses to respiratory stimuli.Design: Adult male mice were implanted for sleep state recordings and thenrandomly assigned to4-5weeks of either orbital platform sleep fragmentation (30events/hr) or control conditions followed by a recovery period.Measurements:We test the sleep propensity, using a murine multiple sleep latencytest (Mmslt), measures were obtained at baseline, within weeks1and5of sleepfragmentation or control condition, and again after2wks recovery. The threshold ofthe stimuli caused by sound and air flow were obtained at baseline and weeks2.Results:short-term SF (1week) resulted in significant declines in the mean SOL ascompared to baseline (1week SF:5.89±0.60min, baseline:9.44±0.94, p=0.049).Similar declines occurred with chronic SF (3-5weeks SF:3.80±0.84min, p=0.001).SOL did not progressively decline however, with no significant difference betweenweek1and week3-5SOL (p=0.40, N.S.). In contrast, the Ct mice had no significantchange in SOL times over the course of the study. In summary, sleep fragmentationcauses increased sleep propensity both acutely and chronically.Conclusions:Sleep latency was reduced in sleep-fragmented mice during sleepfragmentation. The wakefulness impairment was a reversible decline with1week ofsleep fragmentation and with3-5weeks of SF, reversing to baseline levels with2weeks of recovery sleep. The effects of sleep fragmentation on wakefulness arelargely, but not fully, reversible. Study Objectives:To investigate effects of different durations of sleep fragmentationand sleep recovery on lateral thalamic orexin and Fos level and quantity in mice. Todiscuss the mechanism of arousal ability impairment caused by sleep fragmentationand test the hypothesis that the orexin system may have a neuromodulatory effect onarousal states.Design: Adult male mice were implanted for sleep state recordings and thenrandomly assigned to4weeks of either orbital platform sleep fragmentation (30events/hr) or control conditions followed by a recovery period (2wk).Measurements:After certain duration of sleep fragmentation or sleep recovery,lateral thalamic orexin and Fos level and quantity were analyzed byimmunofluorescence, the percentage of Fos positive orexin neurons were measured.We also test the orexin level in lateral hypothalamus with Western-blot.Results: There were no significant differences amongCT-RA, CT-CO2, SF-RA andSF-CO2in the cell counts of orexin neuron(sp>0.05).The decreased the percentage ofFos positive cell in orexin neurons were significant differencesamong differentgroups (p<0.05). But had no effect of lateral hypothalamic orexin level inwestern-blot test. In the subgroup of CO2challenge, CO2could increase the Fosexpression in both sleep fragmentation group and control group, and showed thehighest level at CT-CO2group(50.53%). The SF-RA group showed the lowestresult(21.16%), There were significant differences among SF-RA, CT-RA andCT-CO2(p<0.05).Conclusions:Sleep fragmentation did not change the number of orexin neurons, butdecreased the percentage of Fos positive cell in orexin neurons, which means theorexin neurons activity were injured by sleep fragmentation. Orexin system may playan important role in the process that sleep fragmentation impaired the arousal ability.