ArticleBiology of sex differences2025
The impact of chronic intermittent hypoxia on enzymatic activity in memory-associated brain regions of male and female rats.
Article in Biology of sex differences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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7 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Oxidative and Inflammatory Mechanisms Induced by Intermittent Hypoxia Leading to Vascular Alterations in Rodents: A Systematic Review and Meta-Analysis.Oxidative medicine and cellular longevity · 2026Pooled it
- Chronic intermittent hypoxia increases EPSC frequency in median preoptic nucleus neurons through BDNF-TrkB signaling in a sex-dependent manner.Journal of neurophysiology · 2026Article
- Quantitative and morphological analyses reveal microglia-specific neuroinflammation in brain regions linked to cognitive function in ovariectomized and chronic intermittent hypoxia-exposed female rats.Brain, behavior, & immunity - health · 2026Article
- MiR-106a-5p in extracellular vesicles derived from alveolar epithelial cells mediates cognitive dysfunction induced by chronic intermittent hypoxia in mice through MAPK signaling pathway.Journal of neuroinflammation · 2025Article
- Chronic intermittent hypoxia modulates corneal fibrotic markers and inflammatory cytokine expression in a sex-dependent manner.Experimental eye research · 2025Article
- Kisspeptin-10 Prevents the Development of Cerebral Aneurysms by Reducing the Expression of Egr-1.CNS neuroscience & therapeutics · 2025Article
- ADAM17 Inhibition Protects Cognition in Intermittent Hypoxia: The Role of TREM2.Nature and science of sleep · 2025Article
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Abstract
backgroundObstructive sleep apnea (OSA) is an intermittent hypoxia disorder associated with cognitive dysfunction, including learning and memory impairments. There is evidence that alterations in protease activity and neuronal activation are associated with cognitive dysfunction, are dependent on sex, and may be brain region-specific. However, the mechanisms mediating OSA-induced cognitive impairments are unclear. Therefore, we used a rat model of OSA, chronic intermittent hypoxia (CIH) to investigate protease activity (e.g., calpain and caspase-3) on spectrin, a cytoskeletal protein associated with neurotransmitter release, and neuronal activation (early growth response protein 1, EGR-1) in brain regions associated with learning and memory.
methodsMale and female Sprague Dawley rats were exposed to CIH or room air (normoxic) for 14 days. We quantified protease activity and cleaved spectrin products, along with EGR-1 protein expression in hippocampal subregions (CA1, CA3), cortical regions [entorhinal cortex (ETC), retrosplenial cortex (RSC), cerebellar cortex (CC)], and subcortical regions [raphe nucleus (RN), locus coeruleus (LC)] associated with learning and memory. Within each group, Pearson correlations of calpain activity, caspase-3 activity, and EGR-1 expression were performed between brain regions. Sex differences within normoxic and CIH correlations were examined.
resultsCIH dysregulated calpain activity in male ETC, and female CA1 and RSC. CIH dysregulated caspase-3 activity in male RN, and female CA1 and RSC. CIH decreased calpain and caspase-3 cleavage products in male ETC. CIH decreased calpain-cleaved spectrin in male RSC but increased these products in female RSC. EGR-1 expression was decreased in male and female RN. Correlational analysis revealed CIH increased excitatory connections in males and increased inhibitory connections in females. EGR-1 expression in males shifted from negative to positive correlations.
conclusionsOverall, these data indicate CIH dysregulates protease activity and impairs neuronal function in a brain region- and sex-dependent manner. This indicates that males and females exhibit sex-specific vulnerabilities to mild OSA. These findings concur with our previous behavioral studies that demonstrated memory impairment in CIH-exposed rats.
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