The innate immune toll-like-receptor-2 modulates the depressogenic and anorexiolytic neuroinflammatory response in obstructive sleep apnoea
Dora Polšek, Diana Cash, Mattia Veronese, Katarina Ilić, Tobias Wood, Milan Milošević, Svjetlana Kalanj Bognar, Mary J. Morrell, Steven Williams, Srečko Gajović, Guy D. Leschziner, Dinko Mitrečić, Ivana Rosenzweig
Abstract
Abstract 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.