Male Mice Expressing Human APOE4 Genotype Exhibit Greater Baseline Respiratory Rate and Less Robust Hypoxic Ventilatory Response Than APOE3 Mice as Measured by Whole Body Plethysmography

• DOI: 10.1096/fasebj.2022.36.s1.r4661
• Publication Date: 2022-05-03T09:15:06Z
• Authors: Chase E. Taylor; Jessica S. Newton; Chris M. Calulot; Aaron L. Silverstein; Lydia E. Strattan; Lance A. Johnson; Warren J. Alilain
• Keywords: Hypoxic ventilatory response; Respiratory Rate; Apolipoprotein E; Intermittent hypoxia; Hypoxia

Breathing is vital for life and both uniquely complex vulnerable to disruption. Disorders of breathing such as those that occur in sleep apnea even high cervical spinal cord injury (SCI) can impair quality potentiate the ill effects comorbidities like Alzheimer's disease (AD). Indeed, studies have shown greater cognitive cardiovascular impairments subjects with AD. Apolipoprotein E (ApoE) a ubiquitous protein found throughout body CNS which aids regulation transport cholesterol lipids. Moreover, E4 allele confers higher risk early onset AD than either E2 or E3 alleles. Previous research our lab has interaction between ApoE genotype sex differentially affects motor plasticity following SCI mice. However, it unknown how baseline respiratory pattern capability during hypoxic challenge may differ uninjured individuals expressing APOE4 Thus, APOE independent variable, we measured parameters male targeted replacement mice using whole plethysmography (WBP), hypothesizing animals would display more adaptive, heightened response exposure E4. Preliminary data comparing (n=9) (n=8) demonstrated differences across several key measurements. At baseline, were breathe an energy inefficient manner exemplified measures tidal volume frequency. During sustained hypoxia, frequency, volume, minute initially increased all animals, but APOE3 mounted much robust values falling well below prior termination hypoxia. These preliminary results suggest critical role conditions possessing confer vulnerabilities function environmental challenges leading decline. Future directions include examining anatomically regions neural cell function.