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An improved model of moderate sleep apnoea for investigating its effect as a comorbidity on neurodegenerative disease
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Roberts, Reno, Wall, Mark J., Braren, Ingke, Dhillon, Karendeep, Evans, Amy, Dunne, Jack, Nyakupinda, Simbarashe and Huckstepp, Robert T. R. (2022) An improved model of moderate sleep apnoea for investigating its effect as a comorbidity on neurodegenerative disease. Frontiers in Aging Neuroscience, 14 . 861344. doi:10.3389/fnagi.2022.861344 ISSN 1663-4365.
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Official URL: http://dx.doi.org/10.3389/fnagi.2022.861344
Abstract
Sleep apnoea is a highly prevalent disease that often goes undetected and is associated with poor clinical prognosis, especially as it exacerbates many different disease states. However, most animal models of sleep apnoea (e.g., intermittent hypoxia) have recently been dispelled as physiologically unrealistic and are often unduly severe. Owing to a lack of appropriate models, little is known about the causative link between sleep apnoea and its comorbidities. To overcome these problems, we have created a more realistic animal model of moderate sleep apnoea by reducing the excitability of the respiratory network. This has been achieved through controlled genetically mediated lesions of the preBötzinger complex (preBötC), the inspiratory oscillator. This novel model shows increases in sleep disordered breathing with alterations in breathing during wakefulness (decreased frequency and increased tidal volume) as observed clinically. The increase in dyspnoeic episodes leads to reduction in REM sleep, with all lost active sleep being spent in the awake state. The increase in hypoxic and hypercapnic insults induces both systemic and neural inflammation. Alterations in neurophysiology, an inhibition of hippocampal long-term potentiation (LTP), is reflected in deficits in both long- and short-term spatial memory. This improved model of moderate sleep apnoea may be the key to understanding why this disorder has such far-reaching and often fatal effects on end-organ function.
| Item Type: | Journal Article | |||||||||
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| Subjects: | R Medicine > RC Internal medicine | |||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||
| Library of Congress Subject Headings (LCSH): | Sleep apnea syndromes, Nervous system -- Degeneration, Sleep deprivation | |||||||||
| Journal or Publication Title: | Frontiers in Aging Neuroscience | |||||||||
| Publisher: | Frontiers Research Foundation | |||||||||
| ISSN: | 1663-4365 | |||||||||
| Official Date: | 29 June 2022 | |||||||||
| Dates: |
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| Volume: | 14 | |||||||||
| Article Number: | 861344 | |||||||||
| DOI: | 10.3389/fnagi.2022.861344 | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||
| Date of first compliant deposit: | 1 July 2022 | |||||||||
| Date of first compliant Open Access: | 1 July 2022 | |||||||||
| RIOXX Funder/Project Grant: |
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