Sex and APOE Genotype Influence Respiratory Function Under Hypoxic and Hypoxic-Hypercapnic Conditions

• Published in: Journal of neurophysiology Vol. 132; no. 1; pp. 23 - 33
• Main Authors: Taylor, Chase E, Mendenhall, Laura E, Sunshine, Michael D, Wilson, Jessica N, Calulot, Chris M, Sun, Ramon C, Johnson, Lance A, Alilain, Warren J
• Format: Journal Article
• Language: English
• Published: United States 01.07.2024
• Subjects: Hypercapnia; Hypoxia; APOE; Breathing; Sex
• ISSN: 0022-3077; 1522-1598; 1522-1598
• DOI: 10.1152/jn.00255.2023

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.