Study of Sleep Disturbances In Rett Syndrome By Mecp2-Deficient Mice

[Purpose] Rett syndrome (RTT) is a neurodevelopmental disorder characterized by a variety of neurological symptoms that is mainly caused by MeCP2 mutations and occurs mainly in girls. In particular, sleep disturbance, which is a complication in more than 80% of patients, is a clinical problem that not only decreases the quality of life of the patient but also increases the burden on the caregiver. However, few studies have analyzed sleep pathology in detail, not only in patients but also in RTT mouse models. [Methods] MeCP2-deficient mice were housed in a temperature- and humidity-controlled room under a 12-hour light-dark cycle and free feeding. 7- to 8-week-old wild-type (WT) and MeCP2-deficient mice were evaluated for free activity in the light-dark cycle and non-invasively measured sleep and wakefulness. Sleep evaluation was performed. In addition, gene expression in the hypothalamus was analyzed to determine the mechanism by which MeCP2 deficiency affects circadian rhythm. [Results] Compared to WT mice, MeCP2-deficient mice showed a decrease in activity level as the disease progressed, but circadian rhythms were generally preserved. On the other hand, MeCP2-deficient mice showed much sleep fragmentation in both light and dark periods. Analysis of gene expression in the hypothalamic region, which controls circadian rhythms and sleep/wake, revealed abnormal expression of genes involved in sleep and in vivo rhythm formation. [Conclusion] We are now continuing to analyze the detailed mechanisms of sleep pathology in RTT based on the changes in gene expression related to sleep/wake and circadian rhythms in MeCP2-deficient mice.