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The innate immune toll-like-receptor-2 modulates the depressogenic and anorexiolytic neuroinflammatory response in obstructive sleep apnoea.

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.

SUBMITTER: Polsek D

PROVIDER: S-EPMC7351955 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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The innate immune toll-like-receptor-2 modulates the depressogenic and anorexiolytic neuroinflammatory response in obstructive sleep apnoea.

Polsek Dora D Cash Diana D Veronese Mattia M Ilic Katarina K Wood Tobias C TC Milosevic Milan M Kalanj-Bognar Svjetlana S Morrell Mary J MJ Williams Steve C R SCR Gajovic Srecko S Leschziner Guy D GD Mitrecic Dinko D Rosenzweig Ivana I

Scientific reports 20200710 1

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 ou ...[more]

PMID: 32651433

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Project description:The roles of central nervous mechanisms and cortical output in obstructive sleep apnoea remain unclear. We addressed corticomuscular coupling between cortical sensorimotor areas and lower facial motor units as a mechanistic pathway and as a possible surrogate marker of corticoperipheral motor control in obstructive sleep apnoea. In this exploratory cross-sectional retrospective study, we analysed EEG (C3 and C4 leads) and chin EMG from polysomnography recordings in 86 participants (22 females; age range: 26-81?years): 27 with mild (respiratory disturbance index = 5-15 events/h), 21 with moderate (15-30 events/h) and 23 with severe obstructive sleep apnoea (>30 events/h) and 15 control subjects (<5 events/h). By computing C3-/C4-EEG-chin EMG coherence of signal dynamics in time and frequency domains, we investigated corticomuscular coupling between cortical sensorimotor areas and lower facial motor units with increasing obstructive sleep apnoea severity during the entire sleeping time, during different sleep stages and during obstructive respiratory events, including 5?s before (stable breathing) and after events (breathing resumption). In addition, we studied a possible influence of body mass index and autonomic nervous system activation. We found that both average and respiratory event-specific corticomuscular coupling between cortical sensorimotor areas and lower facial motor units weakened significantly with increasing obstructive sleep apnoea severity, was strongest during N3 and weakened in N1, N2 and rapid eye movement stages (in decreasing order). Coupling increases significantly during the obstructive respiratory events compared with coupling just before and following them. Results were independent of body mass index or autonomic nervous system activation. We conclude that obstructive respiratory events in obstructive sleep apnoea are very strongly associated both quantitatively and temporally with the degree of disconnection within the cortical sensorimotor areas-lower facial motor units pathway. This quite coordinated activity pattern suggests a cortical sensorimotor area-driven obstructive respiratory event pattern generator and a central motor output disorder in obstructive sleep apnoea.

Dataset Information

The innate immune toll-like-receptor-2 modulates the depressogenic and anorexiolytic neuroinflammatory response in obstructive sleep apnoea.

Publications

The innate immune toll-like-receptor-2 modulates the depressogenic and anorexiolytic neuroinflammatory response in obstructive sleep apnoea.

Similar Datasets

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