Sleep and Brain Plasticity Centre, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London (KCL), De Crespigny Park, Box 089, London, SE5 8AF, UK.
University of Zagreb School of Medicine, Croatian Institute for Brain Research, Zagreb, Croatia.
Sci Rep. 2020 Jul 10;10(1):11475. doi: 10.1038/s41598-020-68299-2.
The increased awareness of obstructive sleep apnoea's (OSA) links to Alzheimer's disease and major psychiatric disorders has recently directed an intensified search for their potential shared mechanisms. We hypothesised that neuroinflammation and the microglial TLR2-system may act as a core process at the intersection of their pathophysiology. Moreover, we postulated that inflammatory-response might underlie development of key behavioural and neurostructural changes in OSA. Henceforth, we set out to investigate effects of 3 weeks' exposure to chronic intermittent hypoxia in mice with or without functional TRL2 (TLR2, C57BL/6-Tyrc-Brd-Tg(Tlr2-luc/gfp)Kri/Gaj;TLR2,C57BL/6-Tlr2tm1Kir). By utilising multimodal imaging in this established model of OSA, a discernible neuroinflammatory response was demonstrated for the first time. The septal nuclei and forebrain were shown as the initial key seed-sites of the inflammatory cascade that led to wider structural changes in the associated neurocircuitry. Finally, the modulatory role for the functional TLR2-system was suggested in aetiology of depressive, anxious and anorexiolytic symptoms in OSA.
阻塞性睡眠呼吸暂停（OSA）与阿尔茨海默病和主要精神障碍之间联系的认识不断提高，最近促使人们更加深入地研究它们潜在的共同机制。我们假设神经炎症和小胶质细胞 TLR2 系统可能是其病理生理学交汇点的核心过程。此外，我们推测炎症反应可能是 OSA 中关键行为和神经结构变化发展的基础。因此，我们着手研究在具有或不具有功能性 TLR2（TLR2，C57BL/6-Tyrc-Brd-Tg（Tlr2-luc/gfp）Kri/Gaj；TLR2，C57BL/6-Tlr2tm1Kir）的小鼠中，慢性间歇性缺氧暴露 3 周的影响。通过在 OSA 的这个既定模型中利用多模态成像，首次证明了明显的神经炎症反应。隔核和前脑被证明是炎症级联的最初关键种子部位，导致相关神经回路的广泛结构变化。最后，功能性 TLR2 系统的调节作用被认为在 OSA 中抑郁、焦虑和厌食症状的发病机制中起作用。
