Sex and APOE Genotype Influence Respiratory Function Under Hypoxic and Hypoxic-Hypercapnic Conditions
The apolipoprotein gene has been studied due to its influence on Alzheimer's disease (AD) development and work in an mouse model recently demonstrated impaired respiratory motor plasticity following spinal cord injury (SCI). Individuals with AD often co-present with obstructive sleep apnea (OSA...
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| Published in | Journal of neurophysiology Vol. 132; no. 1; pp. 23 - 33 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
01.07.2024
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| Subjects | |
| Online Access | Get full text |
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| Abstract | The apolipoprotein
gene has been studied due to its influence on Alzheimer's disease (AD) development and work in an
mouse model recently demonstrated impaired respiratory motor plasticity following spinal cord injury (SCI). Individuals with AD often co-present with obstructive sleep apnea (OSA) characterized by cessations in breathing during sleep. Despite the prominence of
genotype and sex as factors in AD progression, little is known about the impact of these variables on respiratory control. Ventilation is tightly regulated across many systems, with respiratory rhythm formation occurring in the brainstem but modulated in response to chemoreception. Alterations within these modulatory systems may result in disruptions of appropriate respiratory control and ultimately, disease. Using mice expressing two different humanized
alleles, we characterized how sex and the presence of
or
influences ventilation during baseline breathing (normoxia) and during respiratory challenge. We show that sex and
genotype influence breathing during hypoxic challenge, which may have clinical implications in the context of AD and OSA. Additionally, female mice, while responding robustly to hypoxia, were unable to recover to baseline respiratory levels, emphasizing sex differences in disordered breathing. |
|---|---|
| AbstractList | This study is the first to use whole body plethysmography (WBP) to measure the impact of APOE alleles on breathing under normoxia and during adverse respiratory challenges in a targeted replacement Alzheimer’s model. Both sex and genotype were shown to affect breathing under normoxia, hypoxic challenge, and hypoxic-hypercapnic challenge. This work has important implications regarding the impact of genetics on respiratory control as well as applications pertaining to conditions of disordered breathing including sleep apnea and neurotrauma.
The apolipoprotein E ( APOE) gene has been studied due to its influence on Alzheimer’s disease (AD) development and work in an APOE mouse model recently demonstrated impaired respiratory motor plasticity following spinal cord injury (SCI). Individuals with AD often copresent with obstructive sleep apnea (OSA) characterized by cessations in breathing during sleep. Despite the prominence of APOE genotype and sex as factors in AD progression, little is known about the impact of these variables on respiratory control. Ventilation is tightly regulated across many systems, with respiratory rhythm formation occurring in the brainstem but modulated in response to chemoreception. Alterations within these modulatory systems may result in disruptions of appropriate respiratory control and ultimately, disease. Using mice expressing two different humanized APOE alleles, we characterized how sex and the presence of APOE3 or APOE4 influences ventilation during baseline breathing (normoxia) and during respiratory challenges. We show that sex and APOE genotype influence breathing during hypoxic challenge, which may have clinical implications in the context of AD and OSA. In addition, female mice, while responding robustly to hypoxia, were unable to recover to baseline respiratory levels, emphasizing sex differences in disordered breathing.
NEW & NOTEWORTHY This study is the first to use whole body plethysmography (WBP) to measure the impact of APOE alleles on breathing under normoxia and during adverse respiratory challenges in a targeted replacement Alzheimer’s model. Both sex and genotype were shown to affect breathing under normoxia, hypoxic challenge, and hypoxic-hypercapnic challenge. This work has important implications regarding the impact of genetics on respiratory control as well as applications pertaining to conditions of disordered breathing including sleep apnea and neurotrauma. The apolipoprotein gene has been studied due to its influence on Alzheimer's disease (AD) development and work in an mouse model recently demonstrated impaired respiratory motor plasticity following spinal cord injury (SCI). Individuals with AD often co-present with obstructive sleep apnea (OSA) characterized by cessations in breathing during sleep. Despite the prominence of genotype and sex as factors in AD progression, little is known about the impact of these variables on respiratory control. Ventilation is tightly regulated across many systems, with respiratory rhythm formation occurring in the brainstem but modulated in response to chemoreception. Alterations within these modulatory systems may result in disruptions of appropriate respiratory control and ultimately, disease. Using mice expressing two different humanized alleles, we characterized how sex and the presence of or influences ventilation during baseline breathing (normoxia) and during respiratory challenge. We show that sex and genotype influence breathing during hypoxic challenge, which may have clinical implications in the context of AD and OSA. Additionally, female mice, while responding robustly to hypoxia, were unable to recover to baseline respiratory levels, emphasizing sex differences in disordered breathing. The apolipoprotein E (APOE) gene has been studied due to its influence on Alzheimer's disease (AD) development and work in an APOE mouse model recently demonstrated impaired respiratory motor plasticity following spinal cord injury (SCI). Individuals with AD often copresent with obstructive sleep apnea (OSA) characterized by cessations in breathing during sleep. Despite the prominence of APOE genotype and sex as factors in AD progression, little is known about the impact of these variables on respiratory control. Ventilation is tightly regulated across many systems, with respiratory rhythm formation occurring in the brainstem but modulated in response to chemoreception. Alterations within these modulatory systems may result in disruptions of appropriate respiratory control and ultimately, disease. Using mice expressing two different humanized APOE alleles, we characterized how sex and the presence of APOE3 or APOE4 influences ventilation during baseline breathing (normoxia) and during respiratory challenges. We show that sex and APOE genotype influence breathing during hypoxic challenge, which may have clinical implications in the context of AD and OSA. In addition, female mice, while responding robustly to hypoxia, were unable to recover to baseline respiratory levels, emphasizing sex differences in disordered breathing.NEW & NOTEWORTHY This study is the first to use whole body plethysmography (WBP) to measure the impact of APOE alleles on breathing under normoxia and during adverse respiratory challenges in a targeted replacement Alzheimer's model. Both sex and genotype were shown to affect breathing under normoxia, hypoxic challenge, and hypoxic-hypercapnic challenge. This work has important implications regarding the impact of genetics on respiratory control as well as applications pertaining to conditions of disordered breathing including sleep apnea and neurotrauma.The apolipoprotein E (APOE) gene has been studied due to its influence on Alzheimer's disease (AD) development and work in an APOE mouse model recently demonstrated impaired respiratory motor plasticity following spinal cord injury (SCI). Individuals with AD often copresent with obstructive sleep apnea (OSA) characterized by cessations in breathing during sleep. Despite the prominence of APOE genotype and sex as factors in AD progression, little is known about the impact of these variables on respiratory control. Ventilation is tightly regulated across many systems, with respiratory rhythm formation occurring in the brainstem but modulated in response to chemoreception. Alterations within these modulatory systems may result in disruptions of appropriate respiratory control and ultimately, disease. Using mice expressing two different humanized APOE alleles, we characterized how sex and the presence of APOE3 or APOE4 influences ventilation during baseline breathing (normoxia) and during respiratory challenges. We show that sex and APOE genotype influence breathing during hypoxic challenge, which may have clinical implications in the context of AD and OSA. In addition, female mice, while responding robustly to hypoxia, were unable to recover to baseline respiratory levels, emphasizing sex differences in disordered breathing.NEW & NOTEWORTHY This study is the first to use whole body plethysmography (WBP) to measure the impact of APOE alleles on breathing under normoxia and during adverse respiratory challenges in a targeted replacement Alzheimer's model. Both sex and genotype were shown to affect breathing under normoxia, hypoxic challenge, and hypoxic-hypercapnic challenge. This work has important implications regarding the impact of genetics on respiratory control as well as applications pertaining to conditions of disordered breathing including sleep apnea and neurotrauma. |
| Author | Mendenhall, Laura E Taylor, Chase E Sunshine, Michael D Calulot, Chris M Alilain, Warren J Sun, Ramon C Wilson, Jessica N Johnson, Lance A |
| Author_xml | – sequence: 1 givenname: Chase E surname: Taylor fullname: Taylor, Chase E organization: Department of Neuroscience, University of Kentucky, Lexington, KY, United States – sequence: 2 givenname: Laura E surname: Mendenhall fullname: Mendenhall, Laura E organization: Department of Neuroscience, University of Kentucky, Lexington, KY, United States – sequence: 3 givenname: Michael D surname: Sunshine fullname: Sunshine, Michael D organization: Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY, United States – sequence: 4 givenname: Jessica N surname: Wilson fullname: Wilson, Jessica N organization: Department of Neuroscience, University of Kentucky, Lexington, KY, United States – sequence: 5 givenname: Chris M surname: Calulot fullname: Calulot, Chris M organization: Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY, United States – sequence: 6 givenname: Ramon C surname: Sun fullname: Sun, Ramon C organization: Department of Biochemistry & Molecular Biology, University of Florida, Gainesville, FL, United States – sequence: 7 givenname: Lance A surname: Johnson fullname: Johnson, Lance A organization: Department of Physiology, University of Kentucky, Lexington, KY, United States – sequence: 8 givenname: Warren J surname: Alilain fullname: Alilain, Warren J organization: University of Kentucky, Lexington, KY, United States |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/38748407$$D View this record in MEDLINE/PubMed |
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| Snippet | The apolipoprotein
gene has been studied due to its influence on Alzheimer's disease (AD) development and work in an
mouse model recently demonstrated impaired... This study is the first to use whole body plethysmography (WBP) to measure the impact of APOE alleles on breathing under normoxia and during adverse... The apolipoprotein E (APOE) gene has been studied due to its influence on Alzheimer's disease (AD) development and work in an APOE mouse model recently... |
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| Title | Sex and APOE Genotype Influence Respiratory Function Under Hypoxic and Hypoxic-Hypercapnic Conditions |
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