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Chronic intermittent hypoxia-mediated cognitive dysfunction in ovariectomized rats.

Emily C Cheung1,2, Joan B Escobar1, Bridget R Alber2

  • 1Department of Pharmacology and Physiology, George Washington University, Washington, District of Columbia, USA.

Experimental Physiology
|May 19, 2025
PubMed
Summary

Obstructive sleep apnoea (OSA) in female rats led to cognitive decline and Alzheimer's disease (AD) markers. This highlights the critical link between OSA, impaired cognition, and AD pathology in women.

Keywords:
Alzheimer's diseaseMorris water mazeobstructive sleep apnoeaovariectomyplethysmographyrespiration

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Area of Science:

  • Neuroscience
  • Cardiorespiratory Medicine
  • Endocrinology

Background:

  • Obstructive sleep apnoea (OSA) is common and linked to cognitive issues.
  • Alzheimer's disease (AD) disproportionately affects women, despite higher OSA prevalence in men.
  • Chronic intermittent hypoxia (CIH), characteristic of OSA, may impact female brain health.

Purpose of the Study:

  • To investigate the effects of CIH on cognitive function in ovariectomized female rats.
  • To examine AD-related pathological markers in the hippocampus following CIH exposure.
  • To assess respiratory function changes associated with CIH in this model.

Main Methods:

  • Ovariectomized Sprague-Dawley rats were exposed to CIH for 26 weeks.
  • Cognitive function was evaluated using the Morris water maze.
  • Hippocampal tissues were analyzed for AD markers, and respiratory function was monitored.

Main Results:

  • CIH exposure significantly impaired spatial learning and memory in female rats (P < 0.0001).
  • Increased total tau protein, an indicator of AD pathology, was observed in the hippocampus (P = 0.0078).
  • CIH-induced respiratory dysfunction, including increased apnoeas, was evident (P = 0.0328).

Conclusions:

  • CIH, mimicking OSA, induces cognitive deficits and AD pathology in female rats.
  • Findings suggest a preclinical link between OSA, cognitive decline, and AD in females.
  • Emphasizes the need for sex-specific research in OSA and Alzheimer's disease.