abstract
- BACKGROUND: Approximately 60% of individuals with Down syndrome (DS) have sleep abnormalities independent of breathing obstruction. Previously, we demonstrated increased wakefulness and decreased NREM sleep in the Dp(16)1Yey + (Dp16) DS model mouse. In this study, we determined if increased RCAN1 levels mediate sleep disruption in Dp16 mice. METHODS: We examined sleep architecture and electroencephalogram (EEG) patterns in young and aged Dp16 mice in which we genetically restored disomic levels of Rcan1 (Dp16 Rcan12N, shortened to Dp16-2 N). Approximately equal numbers of male and female mice were used for each age group. We also examined gene expression and anxiety-like behaviors in aged mice. RESULTS: We found that young Dp16 and Dp16-2 N mice differ slightly from WT mice in sleep architecture and EEG characteristics. However, with age, more severe sleep deficits manifest in Dp16 mice and are partially rescued by Rcan1 dosage correction. Aged Dp16 mice exhibit significantly less mean EEG total power across different sleep states and activity phases. In contrast, WT and Dp16-2 N mice show no age-related differences across states and stages. Aged Dp16 mice diverge from aged WT mice across multiple wake and sleep frequency bands during dark and light phases. In contrast, the EEG characteristics of aged Dp16-2 N differ only modestly from those of WT mice. CONCLUSIONS: Combined, our data demonstrate that restoring Rcan1 gene levels mitigates some sleep architecture disruptions and EEG differences observed in aged Dp16 mice.