Shank3 influences mammalian sleep development

Abstract

Sleep problems are prevalent in Autism Spectrum Disorder (ASD), can be observed before diagnosis and are associated with increased restricted and repetitive behaviors. Therefore, sleep abnormalities may be a core feature, but the developmental trajectory remains unknown. Previously we showed that adult mice with a truncation in Shank3 (Shank3ΔC) recapitulate the ASD sleep phenotype (Ingiosi et al, 2019). In this study we used longitudinal electro-encephalographic recordings to define, for the first time, changes in sleep from weaning to young adulthood in an ASD mouse model. We show that Shank3ΔC mice sleep less throughout their lifespan and have abnormal responses to increased sleep pressure during a specific developmental period. More specifically, mutants appear unable to rapidly enter sleep, despite preceding periods of prolonged waking. Overall, our study indicates that reduced sleep is a core feature of ASD and suggests that problems falling asleep reflect abnormal development in sleep and arousal mechanisms.

The role of selective SATB1 deletion in somatostatin expressing interneurons on endogenous network activity and the transition to epilepsy

“…Several previous studies have concluded that there is a tight correlation between interneuron dysfunction, slow wave sleep (SWS) disturbance and diseases such as epilepsy and neurodevelopmental disorders (Bhat et al, 2014; Lamers et al, 2022; Medina et al, 2022). Close et al (2012) showed that deleting Satb1 from all MGE‐derived interneurons at an early developmental stage (using the Dlx5/6 Cre driver line), and thus causing a reduction of their number, led to electrographic interictal discharges during slow‐wave sleep (SWS).…”

Bridging the translational gap: what can synaptopathies tell us about autism?

“…Hypoactivity and reduced spontaneous locomotor activity have also 10.3389/fnmol.2023.1191323 Frontiers in Molecular Neuroscience 07 frontiersin.org been reported (Drapeau et al, 2018;Kabitzke et al, 2018), as has reduced motor learning (Drapeau et al, 2018) and gait abnormalities (Matas et al, 2021). Sleep patterns have also been examined, and Shank3 mouse models lacking exon 21 have abnormal sleep with earlier onset of diurnal/nocturnal sleep/wake distribution, less sleep overall throughout the lifespan, and take longer to fall sleep as adults (Ingiosi et al, 2019;Medina et al, 2022).…”

“…Clinical/behavioural phenotype N/A • ↑ Repetitive self-grooming (Wang et al, 2011;Yoo et al, 2019;Matas et al, 2021;Ferhat et al, 2023) • ↓ Ultrasonic vocalisations (Peça et al, 2011) • ↑Persistence in unsuccessful social partner engagement (Wang X. et al, 2016) • ↓Sociability and interaction (Peça et al, 2011;Orefice et al, 2019), and no difference in social preference (Drapeau et al, 2018) or social recognition (Kabitzke et al, 2018) • ↓Investigatory behaviour (Wang X. et al, 2016) • Avoidance to novelty (Wang X. et al, 2016) • ↑Anxiety (Wang X. et al, 2016;Bey et al, 2018;Drapeau et al, 2018) • ↓ Sensory motor gating and ↓motor learning (Bey et al, 2018;Drapeau et al, 2018;Yoo et al, 2019) • ↓ Recognition memory (Wang et al, 2011) • ↓Spatial learning (Wang X. et al, 2016, Drapeau et al, 2018 • ↓Striatal-dependent instrumental learning (Wang X. et al, 2016) • Sleep problems (Ingiosi et al, 2019, Medina et al, 2022 • Clinical diagnosis: Neonatal hypotonia, delayed motor milestones, delayed or absent speech, intellectual disability, autism (Phelan et al, 1993;Phelan and McDermid, 2011;Kolevzon et al, 2014) • Bipolar disorder and Psychosis symptom presentations (Kolevzon et al, 2019;Vogels et al, 2021) • Sensory stimulating behaviours (Phelan and McDermid, 2011) and sensory reactivity (Tavassoli et al, 2021) • ↓ Pain perception (Phelan and McDermid, 2011) • ↑ Sleep problems…”