Purpose: Patients with sickle cell disease (SCD) regularly experience abnormal sleep, characterized by frequent arousals and reduced total sleep time. However, obstructive sleep apnea syndrome (OSAS) is a common comorbidity of SCD, making it unclear whether the disease per se is impacting sleep, or sleep disruption is secondary to the presence of OSAS. Thus, we assessed sleep, independent of OSAS, using a mouse model of SCD.
Methods: Sleep was compared between 10-to-12-week-old Townes knockout-transgenic mice with the sickle cell phenotype SS (n = 6) and Townes mice with sickle cell trait AS (n = 6; control). The mice underwent chronic polysomnographic electrode implantation (4EEG/2EMG) to assess sleep architecture.
Results: The SS mice had significantly lower hemoglobin concentration compared to control AS mice (7.3 ± 1.3 vs. 12.9 ± 1.7 g/dL; p < 0.01), consistent with the expected SCD phenotype. SS mice exhibited significantly decreased total NREM sleep time (45.0 ± 0.7 vs. 53.0 ± 1.3% 24 h sleep time; p < 0.01), but no change in total REM sleep time compared to the AS mice. The SS mice took longer to resume sleep after a wake period compared to the AS mice (3.2 ± 0.3 min vs. 1.9 ± 0.2 min; p < 0.05). Unexpectedly, SS mice experienced fewer arousals compared to AS mice (19.0 ± 0.9 vs. 23.3 ± 2.1 arousals/h of sleep; p = 0.031).
Conclusions: The presence of decreased total NREM sleep associated with reduced arousals, in the absence of OSAS, suggests a distinctive underlying sleep phenotype in a mouse model of SCD.
Keywords: Arousals; Hemoglobin; Sickle cell disease; Sleep.