Sleep in Neurodevelopmental Disorders

Esbensen, Anna J.; Schwichtenberg, A. J.

doi:10.1016/bs.irrdd.2016.07.005

Cited by 70 publications

(36 citation statements)

References 182 publications

(275 reference statements)

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“…GO analysis of all 833 DEGs in the mutant hypothalamus following SD suggested, instead, that loss of Snord116 leads to a homeostatic response that relies on several cellular growth processes of the hypothalamus ( Figure 3E). This result indicates that defects in sleep homeostasis in PWS can be derived from development processes of the hypothalamus, as has been described in other neurodevelopmental disorders [57][58][59].…”

Section: Discussionsupporting

confidence: 68%

Paternally expressed imprintedSnord116andPeg3regulate hypothalamic orexin neurons

Marta

Matteo

et al. 2019

Preprint

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words: 186; words count: 9525; figures: 4; Supplementary material: figures 6; table 8Conflict of Interest: each author discloses the absence of any conflicts of interest relative to the research covered in the submitted manuscript. Highlights• Snord116 regulates neuronal activity in the lateral hypothalamus (LH), which is time-locked with cortical states of sleep.• Loss of Snord116 reduces orexin neurons in the LH and affects sleep homeostasis and thermoregulation in mice.• Snord116 and Peg3 independently control orexin expression in the LH.• Paternally expressed alleles maximize the patrilineal effects in the control of REM sleep by the LH in mammals. AbstractImprinted genes are highly expressed in the hypothalamus; however, whether specific imprinted genes affect hypothalamic neuromodulators and their functions is unknown. It has been suggested that Prader-Willi syndrome (PWS), a neurodevelopmental disorder caused by lack of paternal expression at chromosome 15q11-q13, is characterised by hypothalamic insufficiency. Here, we investigate the role of the paternally expressed Snord116 gene within the context of sleep and metabolic abnormalities of PWS, and we report a novel role of this imprinted gene in the function and organisation of the two main neuromodulatory systems of the lateral hypothalamus (LH), namely, the orexin (OX) and melanin concentrating hormone (MCH) systems. We observe that the dynamics between neuronal discharge in the LH and the sleep-wake states of mice with paternal deletion of Snord116 (PWScr m+/p-) are compromised. This abnormal state-dependent neuronal activity is paralleled by a significant reduction in OX neurons in the LH of mutants. Therefore, we propose that an imbalance between OX-and MCH-expressing neurons in the LH of mutants reflects a series of deficits manifested in the PWS, such as dysregulation of rapid eye movement (REM) sleep, food intake and temperature control.

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Section: Discussionsupporting

confidence: 68%

Paternally expressed imprintedSnord116andPeg3regulate hypothalamic orexin neurons

Marta

Matteo

et al. 2019

Preprint

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“…Studies of shift work have demonstrated that sleep deprivation (SD) results in the epigenetic and transcriptional dysregulation of core circadian genes and increased risk for adverse metabolic phenotypes and cancer 13,14 . The epigenetic and metabolic dysregulation associated with SD in healthy individuals provides a basis for understanding these characteristics in the context of neurodevelopmental disorders, which often share a core sleep phenotype among their unique distinguishing features 15 .…”

mentioning

confidence: 99%

Snord116-dependent diurnal rhythm of DNA methylation in mouse cortex

Coulson

Yasui

Dunaway

et al. 2017

Preprint

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Rhythmic oscillations of physiological processes depend on integrating the circadian clock and diurnal environment. DNA methylation is epigenetically responsive to daily rhythms, as a subset of CpG dinucleotides in brain exhibit diurnal rhythmic methylation. A major genetic effect on rhythmic methylation was identified in a mouse Snord116 deletion model of the imprinted disorder Prader-Willi syndrome (PWS). Of the >23,000 diurnally rhythmic CpGs identified in wild-type cortex, 97% lost rhythmic methylation in PWS cortex. Circadian dysregulation of a second imprinted Snord cluster at the Temple/Kagami-Ogata syndrome locus was observed at the level of methylation, transcription, and chromatin, providing mechanistic evidence of crosstalk. Genes identified by diurnal epigenetic changes in PWS mice overlapped rhythmic and PWS-specific genes in human brain and were enriched for PWS-relevant obesity phenotypes and pathways. These results support the proposed evolutionary relationship between imprinting and sleep, and suggest possible chronotherapy in the treatment of PWS and related disorders.Daily and seasonal cycles of light, temperature, and feeding govern energy and activity of organisms from all branches of life. These environmental and metabolic inputs play an important role in the synchronization of the core circadian clock with the rhythmic patterns of many physiological and behavioral processes in peripheral tissues [1][2][3] . The genetically encoded circadian cycle and the environmentally regulated diurnal cycle are integrated by a complex regulatory feedback network which acts at the chromatin, transcriptional, and translational levels to coordinate biological and environmental rhythms [4][5][6] . In mammals, the core circadian clock resides in the suprachiasmatic nucleus of the hypothalamus; however, almost half of all transcripts, both protein-coding and non-coding, exhibit diurnal rhythms in one or more peripheral tissues 7,8 . The epigenetic mechanisms involved in the diurnal rhythms of the cerebral cortex are less well characterized; however, increasing evidence indicates a role for DNA methylation in these rhythms. In contrast to the historically accepted view of DNA methylation as a stably maintained epigenetic mark, approximately 6% (25,476) of CpG sites assayed by 450k array are dynamically regulated throughout diurnal and seasonal cycles 9 . This epigenetic plasticity plays an important role in circadian entrainment and the resiliency of the circadian clock to changes in the diurnal environment [10][11][12] . Studies of shift work have demonstrated that sleep deprivation (SD) results in the epigenetic and transcriptional dysregulation of core circadian genes and increased risk for adverse metabolic phenotypes and cancer 13,14 . The epigenetic and metabolic dysregulation associated with SD in healthy individuals provides a basis for understanding these characteristics in the context of neurodevelopmental disorders, which often share a core sleep phenotype among their unique distinguishing f...

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“…Children with DS frequently experience poor, shorter and disrupted sleep (Esbensen & Schwichtenberg ). This study contributes to our understanding of the practical impact of sleep on the executive functioning of school‐age children with DS, particularly inhibitory control.…”

Section: Discussionmentioning

confidence: 99%