CDKL5 deficiency entails sleep apneas in mice

Area of Science:

• Neuroscience
• Genetics
• Respiratory Medicine

Background:

• Cyclin-dependent kinase-like 5 (CDKL5) disorder is a neurodevelopmental condition with autistic-like behaviors.
• Physiological impacts of CDKL5 disorder, particularly sleep-disordered breathing, are understudied, especially in adults.
• Sleep-disordered breathing is prevalent and serious in Rett syndrome, suggesting a potential link to CDKL5 disorder.

Purpose of the Study:

• To investigate differences in sleep breathing patterns between adult CDKL5 knockout (Cdkl5-KO) and wild-type (WT) mice.
• To determine if sleep apneas are more frequent in mice with CDKL5 deficiency.
• To explore the potential of sleep apnea occurrence as a biomarker for CDKL5 disorder.

Main Methods:

• Utilized whole-body plethysmography for non-invasive recording of sleep and breathing.
• Recorded physiological data for 8 hours during the light period in adult Cdkl5-KO and WT mice.
• Employed receiver operating characteristic (ROC) analysis to differentiate between genotypes based on breathing patterns.

Main Results:

• Sleep apneas occurred significantly more frequently in Cdkl5-KO mice compared to WT mice.
• ROC analysis successfully discriminated between Cdkl5-KO and WT mice based on sleep apnea occurrence.
• Sleep apnea frequency emerged as a significant differentiator between the two groups.

Conclusions:

• Sleep apneas are identified as a core feature of the CDKL5 disorder in a mouse model.
• Sleep-disordered breathing, specifically sleep apnea, can serve as a respiratory biomarker for CDKL5 deficiency.
• Routine evaluation of sleep-disordered breathing is recommended for patients with CDKL5 disorder.