Repeated exposure to severely limited sleep results in distinctive and persistent physiological imbalances in rats

Abstract

Chronic sleep disruption in laboratory rats leads to increased energy expenditure, connective tissue abnormalities, and increased weights of major organs relative to body weight. Here we report on expanded findings and the extent to which abnormalities become long-lasting, potentially permanent changes to health status after apparent recuperation from chronic sleep disruption. Rats were exposed 6 times to long periods of disrupted sleep or control conditions during 10 weeks to produce adaptations and then were permitted nearly 4 months of undisturbed sleep. Measurements were made in tissues from these groups and in preserved tissue from the experimental and control groups of an antecedent study that lacked a lengthy recuperation period. Cycles of sleep restriction resulted in energy deficiency marked by a progressive course of hyperphagia and major (15%) weight loss. Analyses of tissue composition in chronically sleep-restricted rats indicated that protein and lipid amounts in internal organs were largely spared, while adipose tissue depots appeared depleted. This suggests high metabolic demands may have preserved the size of the vital organs relative to expectations of severe energy deficiency alone. Low plasma corticosterone and leptin concentrations appear to reflect low substrate availability and diminished adiposity. After nearly 4 months of recuperation, sleep-restricted rats were consuming 20% more food and 35% more water than did comparison control rats, despite normalized weight, normalized adipocytes, and elevated plasma leptin concentrations. Plasma cholesterol levels in recuperated sleep-restricted rats were diminished relative to those of controls. The chronically increased intake of nutriments and water, along with altered negative feedback regulation and substrate use, indicate that internal processes are modified long after a severe period of prolonged and insufficient sleep has ended.

Figure 1. Dynamic effects on body weight, water intake, and food intake in rats resulting from 6 cycles of sleep restriction or ambulation control conditions followed by an extended recovery period.

Data are expressed as a percentage change from baseline 2-day averages in sleep-restricted (▪) and ambulation control (○) rats. The first 72 days were arranged in 6 cycles, each composed of a 10-day period of sleep restriction or ambulation control (unshaded), followed by a 2-day period of ad libitum sleep (shaded bar). The subsequent 114 days were composed of ad libitum sleep conditions for recuperation (shaded area). See Results section for statistical comparison among groups and across time. Values are means (SE). n = 8 per group, except n = 7 for the sleep-restricted group during the last 2 sleep restriction cycles and during the prolonged recuperation period.

Figure 2. Mean basal plasma corticosterone, insulin, and leptin concentrations in individual ambulation control (○) and sleep-restricted (•) rats without and with an extended recovery period.

Horizontal bars indicate group means for each treatment condition. Significance of *P<0.03 and **P<0.001 are between-group differences during sleep restriction or ambulation control treatments indicated by brackets.