A Drosophila model of sleep restriction therapy for insomnia

Belfer, Samuel J.; Bashaw, Alexander G.; Perlis, Michael L.; Kayser, Matthew S.

doi:10.1038/s41380-019-0376-6

Cited by 15 publications

(13 citation statements)

References 82 publications

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“…1C). To allow for comparison with human sleep measures, we assessed orthologous sleep metrics (22) and found SE to be decreased (Fig. 1D).…”

Section: Kismet Mutants Recapitulate Human Sleep Maintenance Defectsmentioning

confidence: 99%

“…By restricting the sleep opportunity window, SRT enhances sleep drive leading to a more efficient and consolidated sleep. We recently established a model for SRT in flies and demonstrated that SRT in flies improves SE and continuity in short-sleeping Drosophila mutants and a fly model for Alzheimer's disease (22). Whether SRT can reverse sleep defects in neurodevelopmental disorders models is unknown.…”

Section: Sleep Restriction Therapy Restores Sleep Architecture In Glial Kismet Modelsmentioning

confidence: 99%

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The CHD8/CHD7/Kismet family links blood-brain barrier glia and serotonin to ASD-associated sleep defects

et al. 2021

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Sleep disturbances in autism and neurodevelopmental disorders are common and adversely affect patient’s quality of life, yet the underlying mechanisms are understudied. We found that individuals with mutations in CHD8, among the highest-confidence autism risk genes, or CHD7 suffer from disturbed sleep maintenance. These defects are recapitulated in Drosophila mutants affecting kismet, the sole CHD8/CHD7 ortholog. We show that Kismet is required in glia for early developmental and adult sleep architecture. This role localizes to subperineurial glia constituting the blood-brain barrier. We demonstrate that Kismet-related sleep disturbances are caused by high serotonin during development, paralleling a well-established but genetically unsolved autism endophenotype. Despite their developmental origin, Kismet’s sleep architecture defects can be reversed in adulthood by a behavioral regime resembling human sleep restriction therapy. Our findings provide fundamental insights into glial regulation of sleep and propose a causal mechanistic link between the CHD8/CHD7/Kismet family, developmental hyperserotonemia, and autism-associated sleep disturbances.

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“…1C). To allow for comparison with human sleep measures, we assessed orthologous sleep metrics (22) and found SE to be decreased (Fig. 1D).…”

Section: Kismet Mutants Recapitulate Human Sleep Maintenance Defectsmentioning

confidence: 99%

Section: Sleep Restriction Therapy Restores Sleep Architecture In Glial Kismet Modelsmentioning

confidence: 99%

The CHD8/CHD7/Kismet family links blood-brain barrier glia and serotonin to ASD-associated sleep defects

et al. 2021

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“…Insomnia is defined as a purely subjective complaint of dissatisfaction with sleep quality and quantity in spite of adequate opportunity for sleep, which is the most common sleep disorder among adults, especially affecting individuals of advanced age or with neurodegenerative disease. [ 1 ] It is characterized by persistent difficulty initiating or maintaining sleep, along with associated daytime impairment. [ 2 ] As much as one-third of the population experiences transient insomnia symptoms at any given time.…”

Section: Introductionmentioning

confidence: 99%

Guipi decoction for insomnia

Lan

Wen

et al. 2020

Medicine

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Background: Insomnia is a common sleep disorder with symptoms including difficulty falling asleep and early awakening. Guipi decoction is widely used in clinical treatment of insomnia in China. However, there is a lack of systematic evaluation and analysis of Guipi decoction. Therefore, our study will provide efficacy assessments and adverse events assessments. Methods: A comprehensive search for randomized controlled trials of Gupi decoction treatments for insomnia will be carried in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trial (CENTRAL), CINAHL, AMED and Chinese databases include CBM, CNKI, CQVIP, and Wanfang from their inceptions to May 2020. Relevant reference lists, Baidu Scholar and grey literature will also be checked. Two experienced reviewers will independently search all databases. Primary outcomes include Pittsburgh sleep quality index and clinical effective rate, and secondary outcomes include traditional Chinese medicine syndrome, adverse events, and Epworth Sleepiness Scale. Review Manager 5.3 software will be used analyze all data. Results: This article will be dedicated to assessing the efficacy and safety of Guipi decoction for insomnia. Conclusion: The conclusion of this systematic review will provide evidence to judge whether Guipi Decoction is an effective therapeutic intervention for patient with insomnia. Maybe these results could potentially be helpful for improving the therapeutic strategy of patients with insomnia. PROSPERO registration number: CRD 42020164911.

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“…Further, genetic or pharmacological induction of sleep alleviates disease progression in fly models of Alzheimer’s Disease, suggesting that sleep is neuroprotective [16,38,39]. Both sleep and Wallerian degeneration are disrupted in old flies, raising the possibility that restoration of sleep in old animals could protect against age-related decline in glial function [8,36,40]. The identification of sleep-dependent changes in the function and morphology of ensheathing glia will facilitate studies of the effects of sleep on glial function in aging and disease models.…”

Section: Resultsmentioning

confidence: 99%

Sleep regulates the glial engulfment receptor Draper to promote Wallerian degeneration

Stahl

Jaggard

Keene

2019

Preprint

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Highlights 1 2 • Sleep deprivation impairs Wallerian degeneration in fruit flies.• Pharmacological induction of sleep accelerates Wallerian degeneration.• Sleep promotes innervation surrounding damaged neurites by phagocytic glia.• Sleep increases levels of the glial activation markers Draper and Stat92E. 3 Summary 4 Sleep, a universal behavior, is critical for diverse aspects of brain function. Chronic sleep 5 disturbance is associated with numerous health consequences, including neurodegenerative 6 disease and cognitive decline. Neurite damage due to apoptosis, trauma, or genetic factors is a 7 common feature of aging, and clearance of damaged neurons is essential for maintenance of 8 brain function. In the central nervous system, damaged neurites are cleared by Wallerian 9 degeneration, in which activated microglia and macrophages engulf damaged neurons. The fruit 10 fly Drosophila melanogaster provides a powerful model for investigating the relationship 11 between sleep and Wallerian degeneration. Several lines of evidence suggest that glia influence 12 sleep duration, sleep-mediated neuronal homeostasis, and clearance of toxic substances during 13 sleep, raising the possibility that glial engulfment of damaged axons is regulated by sleep. To 14 explore this possibility, we axotomized olfactory receptor neurons and measured the effects of 15 sleep loss or gain on the clearance of damaged neurites. Mechanical sleep deprivation impaired 16 the clearance of damaged neurites, whereas the sleep-promoting drug gaboxadol accelerated 17 clearance. In sleep-deprived animals, multiple markers of glial activation were delayed, 18 including activation of the JAK/STAT pathway, upregulation of the cell corpse engulfment 19 receptor Draper, and innervation of the antennal lobe by glial membranes. These markers were 20 all enhanced when sleep was induced in gaboxadol-treated flies. Taken together, these findings 21 reveal a critical role for sleep in regulation glial activation and engulfment following axotomy, 22 providing a platform for further investigations of the molecular mechanisms underlying sleep-23 dependent modulation of glial function and neurite clearance. Results and Discussion 1 Glial regulation of synaptic function and neuronal homeostasis is critical for proper sleep [1-3]. 2The Drosophila brain contains five distinct types of glia: perineural and subperineural glia, which 3 form the blood-brain barrier; cortex glia; astrocyte-like glia, which regulate synaptic function; and 4 ensheathing glia, which surround neuropil [4][5][6]. Multiple glial subtypes have been identified that 5 regulate sleep in Drosophila [1-3]. Moreover, glial dysfunction is associated with aging, and 6 numerous models of neurodegeneration in flies [7-11]. Despite these bidirectional interactions 7 between glia and sleep, surprisingly little is known about the mechanisms through which sleep-8 deprivation impacts glial function, and how this contributes to neurodegenerative disease. 9 10 Experimental ablation of the antennae results in ax...

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A Drosophila model of sleep restriction therapy for insomnia

Cited by 15 publications

References 82 publications

The CHD8/CHD7/Kismet family links blood-brain barrier glia and serotonin to ASD-associated sleep defects

The CHD8/CHD7/Kismet family links blood-brain barrier glia and serotonin to ASD-associated sleep defects

Guipi decoction for insomnia

Sleep regulates the glial engulfment receptor Draper to promote Wallerian degeneration

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