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High-altitude environments pose significant risks for insomnia development, which severely compromises both physiological health and occupational performance. To elucidate the mechanisms underlying altitude-induced sleep disruption and establish a validated animal model for therapeutic intervention development, we exposed Sprague-Dawley rats to hypobaric hypoxia (5500 m altitude equivalent: 308 mmHg, 20.37% O₂, PiO₂ 8.0 kPa) for 7 days. We employed continuous wireless telemetry to monitor EEG/EMG signals, with concurrent analysis of physiological parameters, blood biochemistry, histopathology, transcriptomics, and protein expression. Quantitative analyses demonstrated decreased caloric intake, transient body mass reduction, and immune-metabolic disturbances. While total sleep duration showed no significant variation, sleep architecture displayed elevated wakefulness periods, reduced active wakefulness, a decreasing trend of slow-wave sleep (SWS), and increased paradoxical sleep (PS) accompanied by attenuated circadian oscillations. The duration of SWS episodes was significantly shortened, indicating a sleep homeostasis imbalance that peaked on day 3. Biochemical profiling revealed reduced levels of antioxidant enzymes, elevated pro-inflammatory cytokines, and hypothalamic–pituitary–adrenal axis activation. Transcriptomic analyses identified the critical involvement of serotonergic/glutamatergic synaptic regulation, lipid metabolism, IL-17 signaling, and cortisol synthesis pathways. Western blot analyses confirmed OX2R upregulation, 5-HT1AR downregulation, and circadian gene dysregulation. Our findings demonstrate that hypobaric hypoxia induces sleep disruption via coordinated mechanisms involving oxidative stress, inflammatory activation, HPA axis hyperactivity, neurotransmitter imbalance, and circadian clock dysfunction, providing a robust preclinical model for mechanistic exploration and therapeutic target identification. Full article

Background: SLC13A5 Citrate Transporter Disorder is a rare pediatric neurodevelopmental disorder. Patients have epilepsy, developmental disability, and impaired mobility. While sleep disorders are common in children with neurodevelopmental disorders, sleep abnormalities have not been reported in SLC13A5 patients. Methods: Here, we assessed sleep disturbances in patients through caregiver reported surveys and in a transgenic mouse model of SLC13A5 deficiency. A total of 26 patients were evaluated with the Sleep Disturbance Scale for Children three times over a one-year span. Sleep and wake activities were assessed in the SLC13A5 knock-out (KO) mice using wireless telemetry devices. Results: A high burden of clinically significant sleep disturbances were reported in the patients, with heterogeneous symptoms that remained stable across time. While sleep disturbances were common, less than 30% of patients were prescribed medications for sleep. Comparatively, in SLC13A5 KO mice using EEG recordings, significant alterations were found during light cycles, when rodents typically sleep. During the sleep period, SLC13A5 mice had increased activity, decreased paradoxical sleep, and changes in absolute power spectral density, indicating altered sleep architecture in the mouse model. Conclusions: Our results demonstrate a significant component of sleep disturbances in SLC13A5 patients and mice, highlighting a potential gap in patient care. Further investigation of sleep dysfunction and the underlying etiologies of sleep disturbances in SLC13A5 citrate transporter disorder is warranted. Full article