Elsevier

Neuroscience

Volume 190, 5 September 2011, Pages 145-155
Neuroscience

Cognitive, Behavioral, and Systems Neuroscience
Research Paper
Chronic sleep restriction causes a decrease in hippocampal volume in adolescent rats, which is not explained by changes in glucocorticoid levels or neurogenesis

https://doi.org/10.1016/j.neuroscience.2011.06.027Get rights and content

Abstract

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.

Highlights

▶Chronic sleep restriction reduces hippocampal volume in adolescent rats. ▶The sleep restriction induced reduction in hippocampal volume is not explained by a decreased neurogenesis. ▶The sleep restriction induced reduction in hippocampal volume is not explained by elevations of the stress hormone corticosterone. ▶Chronic sleep restriction does not affect anxiety levels in rats.

Section snippets

Animals and housing

This study was performed with 48 male Wistar rats, 25 or 28 days old at the start of the experiments. Animals were housed in pairs in a room with a 12 h: 12 h light-dark cycle (lights on 9 am–9 pm) and temperature of 21±1 °C. Standard laboratory chow and water were provided ad libitum. Experiments were approved by the Ethical Committee of Animal Experiments of the University of Groningen.

Experimental design

Two experiments were performed in this study. In the first one, we examined effects of sleep restriction on

Behavior

The rats in the present study coped with the protocol of 1-month SR without visible signs of deterioration or illness. Growth was slightly suppressed in both the sleep-restricted rats and forced-activity controls as compared to the home cage controls, resulting in a significantly lower body weight by the end of the experimental period (SR: 234.6±8.1 g, FA: 222.6±7.1 g, HC: 260.1±6.4 g; treatment effect F2,21=7.01, P=0.005; post hoc Tukey test P<0.05 for both SR and FA vs. HC).

No significant

Discussion

The main finding of this study is that rats subjected to chronic SR during adolescence displayed a 10% reduction in dorsal hippocampal volume. This reduction in size of the hippocampus was not associated with significant changes in survival of newly generated BrdU-labeled cells or changes in DCX expression as a marker of young neurons. Therefore, the volume reduction is not likely explained by a reduction in neurogenesis. During the extended period of SR, the young rats displayed a temporary

Acknowledgments

The authors thank Josè Vidal for helpful suggestions concerning the behavioral tests, Jan Bruggink for performing the radioimmunoassays, Folkert Postema for assistance with the immunochemistry, Jan Keijser for contributing to the immunostaining quantification and Dick Visser for his help with the figures. This study was supported by the Nederlands Organization for Scientific Research (VIDI grant 864.04.002 to P.M.). P.J.L. is supported by the EU (NEURAD), ISAO and the Dutch Brain foundation.

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