title: Chronic sleep restriction during development can lead to long-lasting behavioral effects.
abstract: Sleep abnormalities are highly correlated with neurodevelopmental disorders, and the severity of behavioral abnormalities correlates with the presence of sleep abnormalities. Given the importance of sleep in developmental plasticity, we sought to determine the effects of chronic sleep-restriction during development on subsequent adult behavior. We sleep-restricted developing wild-type mice from P5-P42 for 3h per day by means of gentle handling (n=30) and compared behavioral outputs to controls that were handled 10 min daily (n=33). We assayed activity in the open field, social behavior, repetitive behavior, and anxiety immediately following sleep restriction and after four weeks of recovery. At six weeks of age, immediately following chronic sleep-restriction, mice were less active in an open field arena. Sociability was increased, but repetitive behaviors were unchanged in both males and females. After a 4-week period of recovery, some behavioral abnormalities persisted and some became apparent. Sleep-restricted mice had decreased activity in the beginning of an open field test. Female mice continued to have increased sociability and, in addition, increased preference for social novelty. In contrast, male mice demonstrated decreased sociability with medium effect sizes. Repetitive behavior was decreased in sleep-restricted female mice and increased in males. Measures of anxiety were not affected in the sleep-restricted mice. These results indicate that chronic sleep restriction during development can lead to long-lasting behavioral changes that are modulated by sex. Our study may have implications for a role of disrupted sleep in childhood on the unfolding of neurodevelopmental disorders.
authors.affiliation: Section on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, United States. Electronic address: Rachel.Sare@nih.gov.
authors.forename: R Michelle
authors.initials: RM
authors.lastname: Saré
authors.affiliation: Section on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, United States.
authors.forename: Merlin
authors.initials: M
authors.lastname: Levine
authors.affiliation: Section on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, United States.
authors.forename: Christine
authors.initials: C
authors.lastname: Hildreth
authors.affiliation: Section on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, United States; Advanced MRI Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, United States.
authors.forename: Dante
authors.initials: D
authors.lastname: Picchioni
authors.affiliation: Section on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, United States. Electronic address: beebe@mail.nih.gov.
authors.forename: Carolyn Beebe
authors.initials: CB
authors.lastname: Smith
mesh_terms: D000818:Animals; D001007:Anxiety; D002908:Chronic Disease; D004195:Disease Models, Animal; D005106:Exploratory Behavior; D005260:Female; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D011581:Psychological Tests; D011897:Random Allocation; D012727:Sex Characteristics; D012890:Sleep; D012892:Sleep Deprivation / Q000523:psychology*; D012919:Social Behavior; D013239:Stereotyped Behavior
keywords: Gentle handling; Open field activity; Repetitive behavior; Sleep restriction; Social behavior