Deletion of the Snor D116/S no RD116 alters sleep in mice and patients with Prader-Willi syndrome

Glenda Lassi, Lorenzo Priano, Silvia Maggi, Celina Garcia-Garcia, Edoardo Balzani, Nadia El-Assawy, Marco Pagani, Federico Tinarelli, Daniela Giardino, Alessandro Mauro, Jo Peters, Alessandro Gozzi, Graziano Grugni, Valter Tucci

Research output: Contribution to journalArticle

Abstract

Study Objectives: Sleep-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 (S NO RD116). Here we conducted a translational study into the sleep abnormalities of PWS, testing the hypothesis that S N O R D116 is responsible for sleep defects that characterize the syndrome. Methods: We studied sleep in mutant mice that carry a deletion of Snord 116 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 PWScrm+/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 SNORD 116. We compared the individual EEG parameters of patients with healthy subjects and with a cohort of obese subjects. Results: By studying the mouse mutant line PWScrm+/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 PWScrm+/p- mice we also observed increased body temperature that is coherent with REM sleep alterations in mice and human patients. Conclusions: Our study indicates that paternally expressed Snord 116 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.

Original languageEnglish
Pages (from-to)637-644
Number of pages8
JournalSleep
Volume39
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

Fingerprint

Prader-Willi Syndrome
Sleep
REM Sleep
Brain
Theta Rhythm
Genomic Imprinting
Chromosomes, Human, Pair 7
Human Chromosomes
Body Temperature
Genes
Hippocampus
Healthy Volunteers
Genotype
Magnetic Resonance Imaging
RNA
Temperature

Keywords

  • Prader-Willi
  • Sleep
  • Snord116
  • Temperature
  • Theta rhythms

ASJC Scopus subject areas

  • Physiology (medical)
  • Clinical Neurology

Cite this

Lassi, G., Priano, L., Maggi, S., Garcia-Garcia, C., Balzani, E., El-Assawy, N., ... Tucci, V. (2016). Deletion of the Snor D116/S no RD116 alters sleep in mice and patients with Prader-Willi syndrome. Sleep, 39(3), 637-644. https://doi.org/10.5665/sleep.5542

Deletion of the Snor D116/S no RD116 alters sleep in mice and patients with Prader-Willi syndrome. / Lassi, Glenda; Priano, Lorenzo; Maggi, Silvia; Garcia-Garcia, Celina; Balzani, Edoardo; El-Assawy, Nadia; Pagani, Marco; Tinarelli, Federico; Giardino, Daniela; Mauro, Alessandro; Peters, Jo; Gozzi, Alessandro; Grugni, Graziano; Tucci, Valter.

In: Sleep, Vol. 39, No. 3, 01.03.2016, p. 637-644.

Research output: Contribution to journalArticle

Lassi, G, Priano, L, Maggi, S, Garcia-Garcia, C, Balzani, E, El-Assawy, N, Pagani, M, Tinarelli, F, Giardino, D, Mauro, A, Peters, J, Gozzi, A, Grugni, G & Tucci, V 2016, 'Deletion of the Snor D116/S no RD116 alters sleep in mice and patients with Prader-Willi syndrome', Sleep, vol. 39, no. 3, pp. 637-644. https://doi.org/10.5665/sleep.5542
Lassi, Glenda ; Priano, Lorenzo ; Maggi, Silvia ; Garcia-Garcia, Celina ; Balzani, Edoardo ; El-Assawy, Nadia ; Pagani, Marco ; Tinarelli, Federico ; Giardino, Daniela ; Mauro, Alessandro ; Peters, Jo ; Gozzi, Alessandro ; Grugni, Graziano ; Tucci, Valter. / Deletion of the Snor D116/S no RD116 alters sleep in mice and patients with Prader-Willi syndrome. In: Sleep. 2016 ; Vol. 39, No. 3. pp. 637-644.
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AU - Garcia-Garcia, Celina

AU - Balzani, Edoardo

AU - El-Assawy, Nadia

AU - Pagani, Marco

AU - Tinarelli, Federico

AU - Giardino, Daniela

AU - Mauro, Alessandro

AU - Peters, Jo

AU - Gozzi, Alessandro

AU - Grugni, Graziano

AU - Tucci, Valter

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N2 - Study Objectives: Sleep-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 (S NO RD116). Here we conducted a translational study into the sleep abnormalities of PWS, testing the hypothesis that S N O R D116 is responsible for sleep defects that characterize the syndrome. Methods: We studied sleep in mutant mice that carry a deletion of Snord 116 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 PWScrm+/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 SNORD 116. We compared the individual EEG parameters of patients with healthy subjects and with a cohort of obese subjects. Results: By studying the mouse mutant line PWScrm+/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 PWScrm+/p- mice we also observed increased body temperature that is coherent with REM sleep alterations in mice and human patients. Conclusions: Our study indicates that paternally expressed Snord 116 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.

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