Investigating the Glial Subtype Contributing to Sleep Disturbances in CHARGE Syndrome and Autism Spectrum Disorders
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2018-08-01
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en
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CHARGE Syndrome (CS) and a specific subtype of Autism Spectrum Disorder (ASD) are caused by mutations in the chromatin remodelers CHD7 and CHD8, respectively. Both disorders share common features, one of them is the presence of sleep disturbances. Notably, yeast two-hybrid assays showed a physical interaction between the CHD7 and CHD8 proteins, suggesting their presence in a multisubunit complex in humans. CHD7 and CHD8 have a common ortholog in Drosophila melanogaster, kismet, which has been implicated in circadian regulation. Unpublished data from our lab show that the pan-glial knockdown of kismet results in sleep fragmentation, resembling the sleep deficits observed in CHD7/CHD8 patients. Our aim was to further identify which glial subtype underlies the sleep dysfunction, by specifically knocking down kismet in isolated subtypes and monitoring the resulting activity and sleep. Additionally, we investigated the role of kismet in glia during development at different developmental stages. We identified that the two types of glial cells forming for the blood-brain barrier, subperineurial glia (SPG) and perineurial glia (PG), are the underlying subtypes causing sleep disturbances upon kismet knockdown. A decrease of the mean duration of the sleep episodes, specifically during the dark period was observed with a subsequent increase in the number of sleep episodes. Kismet knockdown in the SPG and PG cells resulted in such fragmented sleep patterns. Our results identify a novel role of the blood brain barrier in the regulation of sleep.
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Faculteit der Sociale Wetenschappen