Age-Associated Development of Sleep Disturbances in db/db Diabetic Mice.

PURPOSE: Disturbed sleep quantity and quality are associated with diabetes and have been recognized as significant risk factors for its development. However, it remains unclear whether sleep disturbances arise during the progression of diabetes and what underlying neurobiological mechanisms may be involved. We aimed to characterize the dynamic development of sleep-wake phenotype in diabetic db/db mice and to investigate the associated neural mechanisms. METHODS: Polysomnographic recordings were conducted to characterize age-dependent changes in sleep-wake characteristics in diabetic db/db mice aged 2 to 6 months. Transcriptomic analyses of brain tissues were performed to investigate the underlying neural mechanisms associated with sleep alterations. RESULTS: Although hyperglycemia was present in db/db mice at 2 months of age, significant fragmentation of non-rapid eye movement (NREM) sleep began at 3 months of age. The total amount of NREM sleep remained unchanged during light phase but was disrupted by an increased frequency of microarousal episodes lasting ≤ 8 s. The darkness-induced wakefulness response progressively declined from 3 months of age and was markedly attenuated by 6 months. Transcriptomic analyses revealed pronounced dysregulation of genes associated with sleep-wake regulation in subcortical regions at 3 months of age. CONCLUSION: These results indicate that diabetes contributes to fragmented sleep and impaired diurnal rhythmicity by influencing sleep-wake regulatory systems in subcortical brain regions.