Hyperactivity and male-specific sleep deficits in the 16p11.2 deletion mouse model of autism
| Autor: | Thomas Nickl-Jockschat, Adam Watson, Kyle S. Krainock, Christopher C. Angelakos, W. Timothy O'Brien, Ted Abel |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.diagnostic_test General Neuroscience Polysomnography medicine.disease Sleep in non-human animals Non-rapid eye movement sleep 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Endocrinology Internal medicine mental disorders Genetic model Chromosomal region medicine Autism Wakefulness Neurology (clinical) Psychology Neuroscience 030217 neurology & neurosurgery Genetics (clinical) Genetic association |
| Zdroj: | Autism Research. 10:572-584 |
| ISSN: | 1939-3792 |
| DOI: | 10.1002/aur.1707 |
| Popis: | Sleep disturbances and hyperactivity are prevalent in several neurodevelopmental disorders, including autism spectrum disorders (ASDs) and attention deficit-hyperactivity disorder (ADHD). Evidence from genome-wide association studies indicates that chromosomal copy number variations (CNVs) are associated with increased prevalence of these neurodevelopmental disorders. In particular, CNVs in chromosomal region 16p11.2 profoundly increase the risk for ASD and ADHD, disorders that are more common in males than females. We hypothesized that mice hemizygous for the 16p11.2 deletion (16p11.2 del/+) would exhibit sex-specific sleep and activity alterations. To test this hypothesis, we recorded activity patterns using infrared beam breaks in the home-cage of adult male and female 16p11.2 del/+ and wildtype (WT) littermates. In comparison to controls, we found that both male and female 16p11.2 del/+ mice exhibited robust home-cage hyperactivity. In additional experiments, sleep was assessed by polysomnography over a 24-hr period. 16p11.2 del/+ male, but not female mice, exhibited significantly more time awake and significantly less time in non-rapid-eye-movement (NREM) sleep during the 24-hr period than wildtype littermates. Analysis of bouts of sleep and wakefulness revealed that 16p11.2 del/+ males, but not females, spent a significantly greater proportion of wake time in long bouts of consolidated wakefulness (greater than 42 min in duration) compared to controls. These changes in hyperactivity, wake time, and wake time distribution in the males resemble sleep disturbances observed in human ASD and ADHD patients, suggesting that the 16p11.2 del/+ mouse model may be a useful genetic model for studying sleep and activity problems in human neurodevelopmental disorders. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 572-584. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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