Conserved sleep disturbances in FOXP1 syndrome originate from developmental dysregulation of peptidergic signaling
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ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE293784 | GEO | 2026/01/23
REPOSITORIES: GEO
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Project description:Conserved sleep disturbances in FOXP1 syndrome originate from developmental dysregulation of peptidergic signaling
| PRJNA1246211 | ENA
Project description:FOXP3+ Treg cells are critical for immune tolerance. Genetic deletion of the Forkhead domain containing proteins of the FOXP-subfamily member FOXP1 from Tregs results in impaired function associated with reduced CD25 expression and IL-2 signaling, but to date the only other FOXP family member expressed in Tregs, FOXP4, has been minimally studied. To investigate the potential functional interactions among FOXP family members in Treg cells, we specifically deleted Foxp1, Foxp4 or both in FOXP3+ committed Treg cells in mice. Our findings show that mice with combined, but not individual, deficiency in FOXP1 and FOXP4 exhibit lymphoproliferation, inflammation, autoimmunity, and early lethality. The combined absence of FOXP1 and FOXP4 in Tregs results in an activated/effector-like phenotype with compromised suppressive function in peripheral lymphoid organs, an enhanced germinal center response and proinflammatory cytokine production. We further show that FOXP1 and FOXP4 bind to Il2ra promoter regions to regulate CD25 expression in Tregs. Through pairwise comparison among mouse strains with Treg-specific deletion of Foxp1, Foxp4 or both, our findings indicate a non-redundant but insufficient role of FOXP4 in Treg cell function.
2025-07-08 | GSE300286 | GEO
Project description:The need to sleep is sensed and discharged in a poorly understood process that is homeostatically controlled over time. In flies, different contributions to this process have been attributed to peripheral ppk and central brain neurons, with the former serving as hypothetical inputs to the sleep homeostat and the latter reportedly serving as the homeostat itself. Here we re-evaluate these distinctions in light of new findings using female flies. First, activating neurons targeted by published ppk and brain drivers elicits similar phenotypes - namely sleep deprivation followed by rebound sleep. Second, inhibiting activity or synaptic output with one type of driver suppresses sleep homeostasis induced using the other type of driver. Third, drivers previously used to implicate central neurons in sleep homeostasis unexpectedly also label ppk neurons. Fourth, activating only this subset of co-labeled neurons is sufficient to elicit sleep homeostasis. Thus, many published contributions of central neurons to sleep homeostasis can be explained by previously unrecognized expression of brain drivers in peripheral ppk neurons, most likely those in the legs that promote walking. Lastly, we show that activation of certain non-ppk neurons can also induce sleep homeostasis. Notably, axons of these as well as ppk neurons terminate in the same ventral brain region, suggesting that a previously undefined neural circuit element of a sleep homeostat may lie nearby.SIGNIFICANCE STATEMENT:The biological need(s) that sleep fulfills are unknown, but they are reflected by an animal's ability to compensate for prior sleep loss in a process called sleep homeostasis. Researchers have searched for the neural circuitry that comprises the sleep homeostat so that the information it conveys can shed light on the nature of sleep need. Here we demonstrate that neurons originating outside of the brain are responsible for phenotypes previously attributed to the proposed central brain sleep homeostat in flies. Our results support a revised neural circuit model for sensing and discharging sleep need in which peripheral inputs connect to a sleep homeostat through previously unrecognized neural circuit elements in the ventral brain.
| S-EPMC9302467 | biostudies-literature
Project description:PurposeWe investigated sleep disturbances among cancer survivors compared to similarly aged women without cancer history.MethodsWe identified 2067 women with a history of cancer other than breast or non-melanoma skin cancer at enrollment in the Sister Study, a US-wide cohort of women with a family history of breast cancer. Cancer survivors were matched with up to 5 cancer-free women (N = 9717) on age at enrollment. An index age (for covariate classification) was defined as the age at cancer diagnosis for survivors and the same age for their matched comparators. Sleep disturbances included duration, sleep medication usage, insomnia symptoms, long sleep-latency onset (≥30 min to fall asleep), frequent night awakenings (waking ≥3/night, ≥ 3 times/week), frequent napping (≥ 3 times/week), and a composite outcome of ≥ 1sleep disturbance. Multivariable linear regression (effect estimate, 95% confidence interval (CI)) and logistic regression (odds ratio, OR, 95% CI) were used for continuous and dichotomous outcomes, respectively.ResultsAt enrollment, cancer survivors were on average 13.8 years (range=0, 62) from diagnosis. After adjustment for age at enrollment and depression, diabetes, hypertension, and menopausal status prior to the index age, sleep disturbances were generally not more common among cancer survivors compared to those without cancer. However, among cancer survivors, those > 2 years from diagnosis were more likely to report ≥ 1 sleep disturbance (OR=1.44; 1.07, 1.93) compared to survivors 0-2 years from diagnosis.ConclusionAddressing sleep disturbances may improve well-being for cancer survivors.
| S-EPMC10873004 | biostudies-literature
Project description:BACKGROUND:Wolfram syndrome is a rare disorder associated with diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing and vision loss, and neurodegeneration. Sleep complaints are common but have not been studied with objective measures. Our goal was to assess rates of sleep apnea and objective and self-reported measures of sleep quality, and to determine the relationship of sleep pathology to other clinical variables in Wolfram syndrome patients. METHODS:Genetically confirmed Wolfram syndrome patients were evaluated at the 2015 and 2016 Washington University Wolfram Syndrome Research Clinics. Patients wore an actigraphy device and a type III ambulatory sleep study device and completed the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI) and/or the Pediatric Sleep Questionnaire (PSQ). PSQI and PSQ questionnaire data were compared to a previously collected group of controls. Patients were characterized clinically with the Wolfram Unified Rating Scale (WURS) and a subset underwent magnetic resonance imaging (MRI) for brain volume measurements. RESULTS:Twenty-one patients were evaluated ranging from age 8.9-29.7?years. Five of 17 (29%) adult patients fit the criteria for obstructive sleep apnea (OSA; apnea-hypopnea index [AHI]???5) and all 4 of 4 (100%) children aged 12?years or younger fit the criteria for obstructive sleep apnea (AHI's???1). Higher AHI was related to greater disease severity (higher WURS Physical scores). Higher mixed apnea scores were related to lower brainstem and cerebellar volumes. Patients' scores on the PSQ were higher than those of controls, indicating greater severity of childhood obstructive sleep-related breathing disorders. CONCLUSIONS:Wolfram syndrome patients had a high rate of OSA. Further study would be needed to assess how these symptoms change over time. Addressing sleep disorders in Wolfram syndrome patients would likely improve their overall health and quality of life.
| S-EPMC6679489 | biostudies-literature
Project description:IntroductionSleep is crucial for physical and psychological health, and disturbances are closely linked to psychiatric disorders, making their management essential for improving treatment outcomes and preventing relapse. Although sleep disturbances are implicated in psychopathology of eating disorders, its role in anorexia nervosa (AN) remains unclear. This review aimed to characterise sleep in AN.MethodsA systematic search was conducted in four scientific databases, including papers from inception to 25 May 2024. A machine learning algorithm (ASReview) was utilised to screen titles and abstracts for eligibility. Sleep quantity, architecture, and quality were investigated. Meta-analyses were conducted to investigate the difference between patients with AN and healthy controls (HC) in total sleep time (TST), wake after sleep onset (WASO), sleep onset latency (SOL), sleep efficiency, Sleep Stage 1, 2, slow wave sleep, rapid eye movement (REM) sleep and REM latency. Certainty of evidence was assessed using the GRADE approach.ResultsOut of 67 potentially eligible papers, 31 were included in this review, with 15 in the meta-analyses. Statistically significant average mean differences were found for TST (-32.1 min [95% CI: -50.9, -13.4]), WASO (19.0 min [95% CI: -2.4, 40.3]), and sleep efficiency (-4.4% [95% CI: -7.9, -0.9]). Additionally, Sleep stage 1 was significantly increased (2.4% [95%-CI: 0.05, 4.7]), while REM sleep was reduced (-2.1% [95%-CI: -4.2, -0.02]). Subgroup analysis showed that TST and WASO did not improve significantly after weight restoration.ConclusionSleep in patients with AN is impaired, with lower TST and sleep efficiency, higher WASO, more time in stage 1 sleep, and less in REM. Weight restoration alone may not improve sleep. While more research is needed, substantial accompanying sleep disturbances in AN justifies addressing these in current treatment practice, also because of the chronic character of AN and importance of sleep for long term (mental) health.
| S-EPMC11786938 | biostudies-literature
Project description:BackgroundMenstrual disturbances harm women's health, and general well-being. As growing evidence highlights the relationship between sleep and menstrual disturbances, it is imperative to comprehensively examine the association between sleep and menstrual disturbance considering the multiple dimensions of sleep. This systematic review aims to identify the association between sleep and menstrual disturbances by evaluating using Buysse's sleep health framework.MethodsA comprehensive search of the literature was conducted in PubMed, EMBASE, psychINFO, and CINAHL to identify publications describing any types of menstrual disturbances, and their associations with sleep published between January 1, 1988 to June 2, 2022. Quality assessment was conducted using the Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies. The findings were iteratively evaluated menstrual disturbances and their association with sleep using Buysse's sleep health framework. This framework understands sleep as multidimensional concept and provides a holistic framing of sleep including Satisfaction, Alertness during waking hours, Timing of sleep, Efficiency, and Sleep duration. Menstrual disturbances were grouped into three categories: premenstrual syndrome, dysmenorrhea, and abnormal menstrual cycle/heavy bleeding during periods.ResultsThirty-five studies were reviewed to examine the association between sleep and menstrual disturbances. Premenstrual syndrome and dysmenorrhea were associated with sleep disturbances in sleep health domains of Satisfaction (e.g., poor sleep quality), Alertness during waking hours (e.g., daytime sleepiness), Efficiency (e.g., difficulty initiating/maintaining sleep), and Duration (e.g., short sleep duration). Abnormal menstrual cycle and heavy bleeding during the period were related to Satisfaction, Efficiency, and Duration. There were no studies which investigated the timing of sleep.Conclusions/implicationsSleep disturbances within most dimensions of the sleep health framework negatively impact on menstrual disturbances. Future research should longitudinally examine the effects of sleep disturbances in all dimensions of sleep health with the additional objective sleep measure on menstrual disturbances. This review gives insight in that it can be recommended to provide interventions for improving sleep disturbances in women with menstrual disturbance.
| S-EPMC10474748 | biostudies-literature
Project description:BACKGROUND AND AIM:Predisposing factors place certain individuals at higher risk for insomnia, especially in the presence of precipitating conditions such as stressful life events. Sleep spindles have been shown to play an important role in the preservation of sleep continuity. Lower spindle density might thus constitute an objective predisposing factor for sleep reactivity to stress. The aim of this study was therefore to evaluate the relationship between baseline sleep spindle density and the prospective change in insomnia symptoms in response to a standardized academic stressor. METHODS:Twelve healthy students had a polysomnography recording during a period of lower stress at the beginning of the academic semester, along with an assessment of insomnia complaints using the insomnia severity index (ISI). They completed a second ISI assessment at the end of the semester, a period coinciding with the week prior to final examinations and thus higher stress. Spindle density, amplitude, duration, and frequency, as well as sigma power were computed from C4-O2 electroencephalography derivation during stages N2-N3 of non-rapid-eye-movement (NREM) sleep, across the whole night and for each NREM sleep period. To test for the relationship between spindle density and changes in insomnia symptoms in response to academic stress, spindle measurements at baseline were correlated with changes in ISI across the academic semester. RESULTS:Spindle density (as well as spindle amplitude and sigma power), particularly during the first NREM sleep period, negatively correlated with changes in ISI (p < 0.05). CONCLUSION:Lower spindle activity, especially at the beginning of the night, prospectively predicted larger increases in insomnia symptoms in response to stress. This result indicates that individual differences in sleep spindle activity contribute to the differential vulnerability to sleep disturbances in the face of precipitating factors.
| S-EPMC4322643 | biostudies-literature
Project description: Not available
| S-EPMC11633700 | biostudies-literature
Project description:Associations between sleep disorders and neurological autoimmunity have been notably expanding recently. Potential immune-mediated etiopathogenesis has been proposed for various sleep disorders including narcolepsy, Kleine-Levin syndrome, and Morvan syndrome. Sleep manifestations are also common in various autoimmune neurological syndromes, but may be underestimated as overriding presenting (and potentially dangerous) neurological symptoms often require more urgent attention. Even so, sleep dysfunction has been described with various neural-specific antibody biomarkers, including IgLON5; leucine-rich, glioma-inactivated protein 1 (LGI1); contactin-associated protein 2 (CASPR2); N-methyl-D-aspartate (NMDA)-receptor; Ma2; dipeptidyl-peptidase-like protein-6 (DPPX); alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R); anti-neuronal nuclear antibody type-1 (ANNA-1, i.e., Hu); anti-neuronal nuclear antibody type-2 (ANNA-2, i.e., Ri); gamma-aminobutyric acid (GABA)-B-receptor (GABA-B-R); metabotropic glutamate receptor 5 (mGluR5); and aquaporin-4 (AQP-4). Given potentially distinctive findings, it is possible that sleep testing could potentially provide objective biomarkers (polysomnography, quantitative muscle activity during REM sleep, cerebrospinal fluid hypocretin-1) to support an autoimmune diagnosis, monitor therapeutic response, or disease progression/relapse. However, more comprehensive characterization of sleep manifestations is needed to better understand the underlying sleep disruption with neurological autoimmunity.
| S-EPMC8116412 | biostudies-literature