Metabolic consequences of chronic sleep restriction in rats: changes in body weight regulation and energy expenditure.

Epidemiological studies have shown an association between short or disrupted sleep and an increased risk to develop obesity. In animal studies, however, sleep restriction leads to an attenuation of weight gain that cannot be explained by changes in energy intake. In the present study, we assessed whether the attenuated weight gain under conditions of restricted sleep is a consequence of an overall increase in energy expenditure. Adult male rats were subjected to a schedule of chronic sleep restriction (SR) for 8 days with a 4h window of unrestricted rest per day. Electroencephalogram and electromyogram recordings were performed to quantify the effect of the sleep restriction schedule on sleep-wake patterns. In a separate experiment, we measured sleep restriction-induced changes in body weight, food intake, and regulatory hormones such as glucose, insulin, leptin and corticosterone. To investigate whether a change in energy expenditure underlies the attenuation of weight gain, energy expenditure was measured by the doubly labeled water method from day 5 until day 8 of the SR protocol. Results show a clear attenuation of weight gain during sleep restriction but no change in food intake. Baseline plasma glucose, insulin and leptin levels are decreased after sleep restriction which presumably reflects the nutritional status of the rats. The daily energy expenditure during SR was significantly increased compared to control rats. Together, we conclude that the attenuation of body weight gain in sleep restricted rats is explained by an overall increase in energy expenditure together with an unaltered energy intake.

Early maternal separation has mild effects on cardiac autonomic balance and heart structure in adult male rats.

Early life adverse experiences have long-term physiologic and behavioral effects and enhance stress sensitivity. This study examined the effects of maternal separation (MS) on cardiac stress responsivity and structure in adulthood. Male Wistar rats were separated from the dams for 3 h per day from postnatal days 2 through 15. When exposed to 5-day intermittent restraint stress (IRS) as adults, MS, and control rats showed similar acute modifications of cardiac sympathovagal balance, quantified via heart rate variability analysis. In addition, MS had no effect on cardiac pacemaker intrinsic activity (as revealed by autonomic blockade with scopolamine and atenolol) and did not affect the circadian rhythmicity of heart rate, neither before nor after IRS. However, MS differed from control rats in cardiac parasympathetic drive following IRS, which was heightened in the latter but remained unchanged in the former, both during the light and dark phases of the daily rhythm. The evaluation of adult cardiac structure indicated that stress experienced during a crucial developmental period induced only modest changes, involving cardiomyocyte hypertrophy, increased density of vascular structures, and myocardial fibrosis. The mildness of these functional-structural effects questions the validity of MS as a model for early stress-induced cardiac disease in humans.

Chronic sleep restriction causes a decrease in hippocampal volume in adolescent rats, which is not explained by changes in glucocorticoid levels or neurogenesis.

Sleep loss strongly affects brain function and may even predispose susceptible individuals to psychiatric disorders. Since a recurrent lack of sleep frequently occurs during adolescence, it has been implicated in the rise in depression incidence during this particular period of life. One mechanism through which sleep loss may contribute to depressive symptomatology is by affecting hippocampal function. In this study, we examined the effects of sleep loss on hippocampal integrity at young age by subjecting adolescent male rats to chronic sleep restriction (SR) for 1 month from postnatal day 30 to 61. They were placed in slowly rotating drums for 20 h per day and were allowed 4 h of rest per day at the beginning of the light phase. Anxiety was measured using an open field and elevated plus maze test, while saccharine preference was used as an indication of anhedonia. All tests were performed after 1 and 4 weeks of SR. We further studied effects of SR on hypothalamic-pituitary-adrenal (HPA) axis activity, and at the end of the experiment, brains were collected to measure hippocampal volume and neurogenesis. Behavior of the SR animals was not affected, except for a transient suppression of saccharine preference after 1 week of SR. Hippocampal volume was significantly reduced in SR rats compared to home cage and forced activity controls. This volume reduction was not paralleled by reduced levels of hippocampal neurogenesis and could neither be explained by elevated levels of glucocorticoids. Thus, our results indicate that insufficient sleep may be a causal factor in the reductions of hippocampal volume that have been reported in human sleep disorders and mood disorders. Since changes in HPA activity or neurogenesis are not causally implicated, sleep disturbance may affect hippocampal volume by other, possibly more direct mechanisms.