Durative sleep fragmentation with or without hypertension suppress rapid eye movement sleep and generate cerebrovascular dysfunction
Xue Na Yanga✉, Jie Ying Tanga, Miaoyi Zhanga, Yifan Heb, Jianhui Fua c✉, Fengfei Dingb d✉
- aDepartment of Neurology, Huashan Hospital, Fudan University, Shanghai 200032, China
- bDepartment of Pharmacology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China
- cDepartment of Neurology, Huashan Hospital, Fudan University, Shanghai 200032, China. Electronic address: jianhuifu@126.com
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Abstract
Either hypertension or chronic insomnia is the risk factor of developing vascular dementia. Durative hypertension can induce vascular remodeling and is used for modeling small vessel disease in rodents. It remains undetermined if the combination of hypertension and sleep disturbance exacerbates vascular dysfunction or pathologies. Previously, we found chronic sleep fragmentation (SF) dampened cognition in young mice without disease predispositions. In the current study, we superimposed SF with hypertension modeling in young mice. Angiotensin II (AngII)-releasing osmotic mini pumps were subcutaneously implanted to generate persistent hypertension, while sham surgeries were performed as controls. Sleep fragmentation with repetitive arousals (10 s every 2 min) during light-on 12 h for consecutive 30 days, while mice undergoing normal sleep (NS) processes were set as controls. Sleep architectures, whisker-stimulated cerebral blood flow (CBF) changes, vascular responsiveness as well as vascular pathologies were compared among normal sleep plus sham (NS + sham), SF plus sham (SF + sham), normal sleep plus AngII (NS + AngII), and SF plus AngII (SF + AngII) groups. SF and hypertension both alter sleep structures, particularly suppressing REM sleep. SF no matter if combined with hypertension strongly suppressed whisker-stimulated CBF increase, suggesting the tight association with cognitive decline. Hypertension modeling sensitizes vascular responsiveness toward a vasoactive agent, Acetylcholine (ACh, 5 mg/ml, 10 μl) delivered via cisterna magna infusion, while SF exhibits a similar but much milder effect. None of the modeling above was sufficient to induce arterial or arteriole vascular remodeling, but SF or SF plus hypertension increased vascular network density constructed by all categories of cerebral vessels. The current study would potentially help understand the pathogenesis of vascular dementia, and the interconnection between sleep and vascular health.
TL;DRSleep architectures, whisker-stimulated cerebral blood flow (CBF) changes, vascular responsiveness as well as vascular pathologies were compared and chronic sleep fragmentation (SF) dampened cognition in young mice without disease predispositions was found to help understand the pathogenesis of vascular dementia, and the interconnection between sleep and vascular health. (Semantic Scholar)