An Improved Model of Moderate Sleep Apnoea for Investigating Its Effect as a Comorbidity on Neurodegenerative Disease
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 u...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2022.861344/full |
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| author | Reno Roberts Mark J. Wall Ingke Braren Karendeep Dhillon Amy Evans Jack Dunne Simbarashe Nyakupinda Robert T. R. Huckstepp |
| author_facet | Reno Roberts Mark J. Wall Ingke Braren Karendeep Dhillon Amy Evans Jack Dunne Simbarashe Nyakupinda Robert T. R. Huckstepp |
| author_sort | Reno Roberts |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T13:47:02Z |
| format | Article |
| id | doaj.art-bafce341b9d74d1bb23a4a8bd42b909a |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-12T13:47:02Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-bafce341b9d74d1bb23a4a8bd42b909a2022-12-22T00:22:40ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652022-06-011410.3389/fnagi.2022.861344861344An Improved Model of Moderate Sleep Apnoea for Investigating Its Effect as a Comorbidity on Neurodegenerative DiseaseReno Roberts0Mark J. Wall1Ingke Braren2Karendeep Dhillon3Amy Evans4Jack Dunne5Simbarashe Nyakupinda6Robert T. R. Huckstepp7School of Life Sciences, University of Warwick, Coventry, United KingdomSchool of Life Sciences, University of Warwick, Coventry, United KingdomUniversity Medical Center Eppendorf, Vector Facility, Institute for Experimental Pharmacology and Toxikology, Hamburg, GermanySchool of Life Sciences, University of Warwick, Coventry, United KingdomSchool of Life Sciences, University of Warwick, Coventry, United KingdomSchool of Life Sciences, University of Warwick, Coventry, United KingdomSchool of Life Sciences, University of Warwick, Coventry, United KingdomSchool of Life Sciences, University of Warwick, Coventry, United KingdomSleep 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.https://www.frontiersin.org/articles/10.3389/fnagi.2022.861344/fullcognitive declinesleep apnoea (SA)neuroinflammationneurodegenerationsleep deprivation (SD) |
| spellingShingle | Reno Roberts Mark J. Wall Ingke Braren Karendeep Dhillon Amy Evans Jack Dunne Simbarashe Nyakupinda Robert T. R. Huckstepp An Improved Model of Moderate Sleep Apnoea for Investigating Its Effect as a Comorbidity on Neurodegenerative Disease Frontiers in Aging Neuroscience cognitive decline sleep apnoea (SA) neuroinflammation neurodegeneration sleep deprivation (SD) |
| title | An Improved Model of Moderate Sleep Apnoea for Investigating Its Effect as a Comorbidity on Neurodegenerative Disease |
| title_full | An Improved Model of Moderate Sleep Apnoea for Investigating Its Effect as a Comorbidity on Neurodegenerative Disease |
| title_fullStr | An Improved Model of Moderate Sleep Apnoea for Investigating Its Effect as a Comorbidity on Neurodegenerative Disease |
| title_full_unstemmed | An Improved Model of Moderate Sleep Apnoea for Investigating Its Effect as a Comorbidity on Neurodegenerative Disease |
| title_short | An Improved Model of Moderate Sleep Apnoea for Investigating Its Effect as a Comorbidity on Neurodegenerative Disease |
| title_sort | improved model of moderate sleep apnoea for investigating its effect as a comorbidity on neurodegenerative disease |
| topic | cognitive decline sleep apnoea (SA) neuroinflammation neurodegeneration sleep deprivation (SD) |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2022.861344/full |
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