The Innate Immune Toll-Like Receptor-2 modulates the Depressogenic and Anorexiolytic Neuroinflammatory Response in Obstructive Sleep Apnoea

Abstract

243/250) Background:The neurological mechanisms of the disease process of obstructive sleep apnea, the second most frequent sleep disorder, remain unclear whilst its links with several major neuropsychiatric disorders, such as depression, anxiety and even Alzheimer's disorder, are increasingly recognised. A radical theory, that inflammation in the brain may underlie certain phenotypes of many of these disorders, has been proposed, and the microglial TLR2 system may serve as an important crossroad at the borderlands of several pathogenesis. This study undertook to investigate whether a neuroinflammatory response occurs under conditions of OSA, and whether it might be related to a modulated response due to TLR2 functionality in an established rodent model of OSA. Methods:The effects of three weeks' exposure to chronic intermittent hypoxia were monitored in mice with or without functional TLR2 (C57BL/6-Tyrc-Brd-Tg(Tlr2-luc/gfp)Kri/Gaj; TLR2 -/-, C57BL/6-Tlr2tm1Kir), that were investigated by multimodal in vivo and ex vivo imaging, combining magnetic resonance and bioluminescence imaging and a variety of functional tests. Results:An acute neuroinflammatory response was demonstrated following the three days in the basal forebrain of mice, and more chronically in other parts of the frontal cortex. Adaptive changes in specific neurocircuitry were demonstrated, with significant links to agitated (mal)adaptive behaviour under episodes of stress, and an increased ability to gain weight. Conclusions:Our results suggest that microglial activation and an innate immune response might be the missing link underlying the pathogenesis of well known structural, psychologic and metabolic changes experienced by some patients with OSA.

Neuroplastin in human cognition: review of literature and future perspectives

“…Bidirectional links between both the macro-and micro-architecture of sleep and neuroplasticity have demonstrated its crucial role in the recovery of cognitive functions [44,45]. In view of this fundamental function of sleep, perhaps unsurprisingly, our group has recently demonstrated Np's involvement in recovery from one of the major sleep disorders, obstructive sleep apnea (OSA) [46], a condition linked to anxiety disorders, depression [47,48], and AD [49][50][51], effectively with most of disorders that have so far also been linked with prominent Np plastic response. In our study of a rodent model of OSA, Np's expression appeared to be dependent on the TLR2 functionality [46].…”

“…In view of this fundamental function of sleep, perhaps unsurprisingly, our group has recently demonstrated Np's involvement in recovery from one of the major sleep disorders, obstructive sleep apnea (OSA) [46], a condition linked to anxiety disorders, depression [47,48], and AD [49][50][51], effectively with most of disorders that have so far also been linked with prominent Np plastic response. In our study of a rodent model of OSA, Np's expression appeared to be dependent on the TLR2 functionality [46]. Arguably, this might be reflective of a more important role in the recovery process in the absence of TLR2 and/ or of different mechanisms at play under control conditions.…”