Dataset Information

Loss of Snord116 impacts lateral hypothalamus, sleep, and food-related behaviors.

ABSTRACT: Imprinted 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 characterized 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 significant role of this imprinted gene in the function and organization of the 2 main neuromodulatory systems of the lateral hypothalamus (LH) - namely, the orexin (OX) and melanin concentrating hormone (MCH) - systems. We observed that the dynamics between neuronal discharge in the LH and the sleep-wake states of mice with paternal deletion of Snord116 (PWScrm+/p-) are compromised. This abnormal state-dependent neuronal activity is paralleled by a significant reduction in OX neurons in the LH of mutant mice. Therefore, we propose that an imbalance between OX- and MCH-expressing neurons in the LH of mutant mice reflects a series of deficits manifested in the PWS, such as dysregulation of rapid eye movement (REM) sleep, food intake, and temperature control.

SUBMITTER: Pace M

PROVIDER: S-EPMC7406246 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Loss of Snord116 impacts lateral hypothalamus, sleep, and food-related behaviors.

Pace Marta M Falappa Matteo M Freschi Andrea A Balzani Edoardo E Berteotti Chiara C Lo Martire Viviana V Kaveh Fatemeh F Hovig Eivind E Zoccoli Giovanna G Amici Roberto R Cerri Matteo M Urbanucci Alfonso A Tucci Valter V

JCI insight 20200618 12

Imprinted 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 characterized by hypothalamic insufficiency. Here, we investigate the role of the paternally expressed Snord116 gene within the context of sleep and metabolic abnormalities of PWS, ...[more]

PMID: 32365348

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Project description:Study objectivesSleep-wake disturbances are often reported in Prader-Willi syndrome (PWS), a rare neurodevelopmental syndrome that is associated with paternally-expressed genomic imprinting defects within the human chromosome region 15q11-13. One of the candidate genes, prevalently expressed in the brain, is the small nucleolar ribonucleic acid-116 (SNORD116). Here we conducted a translational study into the sleep abnormalities of PWS, testing the hypothesis that SNORD116 is responsible for sleep defects that characterize the syndrome.MethodsWe studied sleep in mutant mice that carry a deletion of Snord116 at the orthologous locus (mouse chromosome 7) of the human PWS critical region (PWScr). In particular, we assessed EEG and temperature profiles, across 24-h, in PWScr (m+/p-) heterozygous mutants compared to wild-type littermates. High-resolution magnetic resonance imaging (MRI) was performed to explore morphoanatomical differences according to the genotype. Moreover, we complemented the mouse work by presenting two patients with a diagnosis of PWS and characterized by atypical small deletions of SNORD116. We compared the individual EEG parameters of patients with healthy subjects and with a cohort of obese subjects.ResultsBy studying the mouse mutant line PWScr(m+/p-), we observed specific rapid eye movement (REM) sleep alterations including abnormal electroencephalograph (EEG) theta waves. Remarkably, we observed identical sleep/EEG defects in the two PWS cases. We report brain morphological abnormalities that are associated with the EEG alterations. In particular, mouse mutants have a bilateral reduction of the gray matter volume in the ventral hippocampus and in the septum areas, which are pivotal structures for maintaining theta rhythms throughout the brain. In PWScr(m+/p-) mice we also observed increased body temperature that is coherent with REM sleep alterations in mice and human patients.ConclusionsOur study indicates that paternally expressed Snord116 is involved in the 24-h regulation of sleep physiological measures, suggesting that it is a candidate gene for the sleep disturbances that most individuals with PWS experience.

Project description:Background Measures to protect against the spread of COVID-19 include guidance on personal and environmental hygiene. Some guidelines related to COVID-19 directly align with or have similarity to evidence-based food safety practices (FSP) taught in nutrition education classes, including handwashing and washing produce before eating. Objective To understand the impacts of the COVID-19 pandemic on youth handwashing and washing produce before eating behaviors. Study Design, Setting, Participants Data were collected from youth (N = 1,098) in grades 3-5 who participated in SNAP-Education (SNAP-Ed) and the Expanded Food and Nutrition Education Program (EFNEP) in Florida. Utilizing common self-report survey measures, baseline measures from 3 years prior to the pandemic and 3 months during the pandemic were compared for handwashing before eating and washing produce before eating. Due to incomplete data collection during the first 8 months of the pandemic, only behaviors from October 20-January 31 intervals (October 2018- January 2021) were compared to control for seasonal differences. Measurable Outcomes/Analysis Behavioral measures are based on a frequency scale from 1 to 4 (4 being the most frequent). An independent samples t test was used to compare baseline FSP scores from intervals before and during the pandemic. Results No significant difference was found in the frequency of handwashing before and during COVID-19 (3.16 vs 3.18, respectively; P = 0.76). A significant increase was found in the frequency of washing produce before eating before and during COVID-19 (3.14 vs 3.31, respectively; P = 0.008). Conclusion This study did not find any significant changes in handwashing frequency during COVID-19, however, a significant increase in washing produce prior to eating was found. Handwashing prior to eating is a current CDC guideline for COVID-19 mitigation while washing produce prior to eating is not (CDC 2021). Changes in lifestyle and/or eating arrangements during the pandemic might explain these findings.

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Loss of Snord116 impacts lateral hypothalamus, sleep, and food-related behaviors.

Publications

Loss of Snord116 impacts lateral hypothalamus, sleep, and food-related behaviors.

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