Chronic intermittent hypoxia-mediated cognitive dysfunction in ovariectomized rats

Emily C. Cheung, Department of Pharmacology and Physiology, George Washington University, Washington, District of Columbia, USA.
Joan B. Escobar, Department of Pharmacology and Physiology, George Washington University, Washington, District of Columbia, USA.
Bridget R. Alber, Department of Biomedical Engineering, George Washington University, Washington, District of Columbia, USA.
Caitlin Ribeiro, Department of Pharmacology and Physiology, George Washington University, Washington, District of Columbia, USA.
Ishan Abdullah, Department of Pharmacology and Physiology, George Washington University, Washington, District of Columbia, USA.
Grant Kowalik, Department of Biomedical Engineering, George Washington University, Washington, District of Columbia, USA.
Jeannette Rodriguez, Department of Biomedical Engineering, George Washington University, Washington, District of Columbia, USA.
Grey Harral, Department of Biomedical Engineering, George Washington University, Washington, District of Columbia, USA.
Makeda Melkie, Department of Biomedical Engineering, George Washington University, Washington, District of Columbia, USA.
Aman Gill, Department of Biomedical Engineering, George Washington University, Washington, District of Columbia, USA.
John T. Ketzenberger, Department of Biomedical Engineering, George Washington University, Washington, District of Columbia, USA.
John Bethea, Department of Anatomy and Cell Biology, George Washington University, Washington, District of Columbia, USA.
Vsevolod Y. Polotsky, Department of Anesthesiology and Critical Care Medicine, George Washington University, Washington, District of Columbia, USA.
Vivek Jain, Department of Medicine, George Washington University, Washington, District of Columbia, USA.
Kathryn Schunke, Department of Cell & Molecular Biology, University of Hawaii, Honolulu, Hawai'i, USA.
Matthew W. Kay, Department of Biomedical Engineering, George Washington University, Washington, District of Columbia, USA.
David Mendelowitz, Department of Pharmacology and Physiology, George Washington University, Washington, District of Columbia, USA.

Document Type

Journal Article

Publication Date

5-19-2025

Journal

Experimental physiology

DOI

10.1113/EP092018

Keywords

Alzheimer's disease; Morris water maze; obstructive sleep apnoea; ovariectomy; plethysmography; respiration

Abstract

Obstructive sleep apnoea (OSA) is a prevalent cardiorespiratory disorder associated with significant neurocognitive consequences. Despite the higher prevalence of OSA in men, there is a strong association between OSA and Alzheimer's disease (AD), which disproportionately affects women. This study aimed to investigate the impact of chronic intermittent hypoxia (CIH), a hallmark of OSA, on cognitive function and AD markers in ovariectomized, female rats. At 8 weeks of age, 16 Sprague-Dawley rats underwent ovariectomy and were exposed to CIH for 26 weeks. Cognitive function was assessed using the Morris water maze, revealing significant deficits in spatial learning (P < 0.0001) and memory (P = 0.008) in CIH-exposed rats, compared to controls. Analysis of hippocampal tissue showed increased total tau protein (P = 0.0078), indicative of AD pathology. Additionally, CIH-exposed rats exhibited respiratory dysfunction characterized by increased frequency of apnoeas (P = 0.0328). These findings provide preclinical evidence of the association between OSA, cognitive decline and AD pathology in females, emphasizing the importance of sex-specific research in understanding and addressing these pathophysiological interconnections.

Department

Medicine

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