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 (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.We 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 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 SNORD116. We compared the individual EEG parameters of patients with healthy subjects and with a cohort of obese subjects.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.Our 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.
Scheda prodotto non validato
I dati visualizzati non sono stati ancora sottoposti a validazione formale da parte dello Staff di IRIS, ma sono stati ugualmente trasmessi al Sito Docente Cineca (Loginmiur).
|Titolo:||Deletion of the Snord116/SNORD116 Alters Sleep in Mice and Patients with Prader-Willi Syndrome.|
|Autori:||Lassi, G; Priano, L; Maggi, S; Garcia Garcia, C; Balzani, E; El Assawy, N; Pagani, Marco; Tinarelli, F; Giardino, D; Mauro, A; Peters, J; Gozzi, A; Grugni, G; Tucci, V.|
|Titolo del periodico:||SLEEP|
|Anno di pubblicazione:||2015|
|Appare nelle tipologie:||03.1 Articolo su rivista (Journal article)|