Sex chromosomes regulate nighttime sleep propensity during recovery from sleep loss in mice.

Sex differences in spontaneous sleep amount are largely dependent on reproductive hormones; however, in mice some sex differences in sleep amount during the active phase are preserved after gonadectomy and may be driven by non-hormonal factors. In this study, we sought to determine whether or not these sex differences are driven by sex chromosome complement. Mice from the four core genotype (FCG) mouse model, whose sex chromosome complement (XY, XX) is independent of phenotype (male or female), were implanted with electroencephalographic (EEG) and electromyographic (EMG) electrodes for the recording of sleep-wake states and underwent a 24-hr baseline recording followed by six hours of forced wakefulness. During baseline conditions in mice whose gonads remained intact, males had more total sleep and non-rapid eye movement sleep than females during the active phase. Gonadectomized FCG mice exhibited no sex differences in rest-phase sleep amount; however, during the mid-active-phase (nighttime), XX males had more spontaneous non-rapid eye movement (NREM) sleep than XX females. The XY mice did not exhibit sex differences in sleep amount. Following forced wakefulness there was a change in the factors regulating sleep. XY females slept more during their mid-active phase siestas than XX females and had higher NREM slow wave activity, a measure of sleep propensity. These findings suggest that the process that regulates sleep propensity is sex-linked, and that sleep amount and sleep propensity are regulated differently in males and females following sleep loss

Genotype had an effect on total sleep during the active phase.

<p>24-hr baseline sleep records of GDX FCG mice averaged into 2-hr intervals. Graphs show minutes spent in: (a) total sleep, (b) NREM sleep and (c) REM sleep. Figure (d) shows normalized NREM SWA for 2-hr intervals as percentages of 24-hr SWA. During the dark phase at ZT 16–18 XXM mice consistently exhibited more sleep than XXF mice (indicated by asterisk). Error bars represent mean ± sem. *p<0.05 Tukey posthoc test (XXM≠XXF). Shaded area represents the 12-hr dark phase.</p

2×2 comparisons of FCG mice with intact gonads.

<p>XY mice (XYM; XYF) and XX mice (XXM; XXF) and gonadal males (XYM; XXM) and females (XYF; XXF). Sex differences in TOTAL SLEEP and NREM sleep amount are similar to what was previously reported in intact wild-type mice (Paul et al., 2006). Data are presented mean ± sem.</p

Sleep Deprivation alters the influence of biological sex on active-phase sleep behavior

AbstractPoor sleep is a hazard of daily life that oftentimes cannot be avoided. Gender differences in daily sleep and wake patterns are widely reported; however, it remains unclear how biological sex, which is comprised of genetic and endocrine components, directly influences sleep regulatory processes. In the majority of model systems studied thus far, sex differences in daily sleep amount are predominant during the active (wake) phase of the sleep-wake cycle. The pervasiveness of sex differences in sleep amount throughout phylogeny suggests a strong underlying genetic component. The goal of the current study is to determine if sex differences in active-phase sleep amount are dependent on sex chromosomes in mice.Sleep was examined in the four-core genotype (FCG) mouse model, whose sex chromosome complement (XY, XX) is independent of sex phenotype (male or female). In this line, sex phenotype is determined by the presence or absence of the Sry gene, which is dissociated from the Y chromosome. Polysomnographic sleep recordings were obtained from gonadectomized (GDX) FCG mice to examine spontaneous sleep states and the ability to recover from sleep loss. We report that during the active-phase, the presence of the Sry gene accounts for most sex differences during spontaneous sleep; however, during recovery from sleep loss, sex differences in sleep amount are partially driven by sex chromosome complement. These results suggest that genetic factors on the sex chromosomes encode the homeostatic response to sleep loss.</jats:p

Absolute recovery sleep amount was not sensitive to genotype after sleep loss.

<p>24-hr sleep records of GDX FCG mice during 6 hrs of forced wakefulness and 18 hrs of recovery sleep averaged into 2-hr intervals. Graphs show minutes spent in: (a) total sleep, (b) NREM sleep and (c) REM sleep. During the dark phase at ZT 12–14 XXM mice exhibited more REM sleep than XXF mice (indicated by asterisk). Error bars represent mean ± sem. * p<0.05 Tukey posthoc test (XXM≠XXF). Shaded area represents the 12-hr dark phase.</p

Genotype had effects on recovery sleep amount and slow wave activity normalized to baseline.

<p>18 hrs of recovery sleep amount averaged into 2-hr intervals and then normalized to baseline by expressing the difference in minutes. Graphs show percentage of recovery sleep for (a) total sleep, (b) NREM sleep and (c) REM sleep. Figure (d) shows normalized NREM SWA for 2-hr intervals as percentages of 24-hr SWA. Error bars represent mean ± sem. *p<0.05 Tukey posthoc test (XXM≠XXF). ‡p<0.05 Tukey posthoc test (XYF≠XXF). Shaded area represents the 12-hr dark phase.</p