Circadian Rhythms and Sleep Are Dependent Upon Expression Levels of Key Ubiquitin Ligase Ube3a

Normal neurodevelopment requires precise expression of the key ubiquitin ligase gene Ube3a . Comparing newly generated mouse models for Ube3a downregulation (models of Angelman syndrome) vs. Ube3a upregulation (models for autism), we find reciprocal effects of Ube3a gene dosage on phenotypes associa...

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Vydáno v:	Frontiers in Behavioral Neuroscience Ročník 16; s. 837523
Hlavní autoři:	Shi, Shu-qun, Mahoney, Carrie E., Houdek, Pavel, Zhao, Wenling, Anderson, Matthew P., Zhuo, Xinming, Beaudet, Arthur, Sumova, Alena, Scammell, Thomas E., Johnson, Carl Hirschie
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Switzerland Frontiers Media SA 23.03.2022 Frontiers Research Foundation Frontiers Media S.A
Témata:	Angelman syndrome Angelman's syndrome Animal models Autism Brain research circadian Circadian rhythm Circadian rhythms Dosage Gene dosage Gene expression Genotype & phenotype Imprinting Locomotor activity Neurodevelopment neurodevelopmental disorders Neurons Neuroscience Neurosciences. Biological psychiatry. Neuropsychiatry Phenotypes Physical activity Proteins RC321-571 sleep Sleep deprivation Sleep disorders UBE3A (E6AP) Ubiquitin ubiquitin ligase Ubiquitin-protein ligase UBE3A (E6AP) sleep ubiquitin ligase Angelman syndrome circadian imprinting neurodevelopmental disorders autism
ISSN:	1662-5153, 1662-5153
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Shrnutí:	Normal neurodevelopment requires precise expression of the key ubiquitin ligase gene Ube3a . Comparing newly generated mouse models for Ube3a downregulation (models of Angelman syndrome) vs. Ube3a upregulation (models for autism), we find reciprocal effects of Ube3a gene dosage on phenotypes associated with circadian rhythmicity, including the amount of locomotor activity. Consistent with results from neurons in general, we find that Ube3a is imprinted in neurons of the suprachiasmatic nuclei (SCN), the pacemaking circadian brain locus, despite other claims that SCN neurons were somehow exceptional to these imprinting rules. In addition, Ube3a -deficient mice lack the typical drop in wake late in the dark period and have blunted responses to sleep deprivation. Suppression of physical activity by light in Ube3a -deficient mice is not due to anxiety as measured by behavioral tests and stress hormones; quantification of stress hormones may provide a mechanistic link to sleep alteration and memory deficits caused by Ube3a deficiency, and serve as an easily measurable biomarker for evaluating potential therapeutic treatments for Angelman syndrome. We conclude that reduced Ube3a gene dosage affects not only neurodevelopment but also sleep patterns and circadian rhythms.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors share first authorship This article was submitted to Individual and Social Behaviors, a section of the journal Frontiers in Behavioral Neuroscience Edited by: Emi Hasegawa, University of Tsukuba, Japan Reviewed by: Li Wang, Children’s National Hospital, United States; Ling Shan, Netherlands Institute for Neuroscience (KNAW), Netherlands
ISSN:	1662-5153 1662-5153
DOI:	10.3389/fnbeh.2022.837523