Evidence mapPaperPMID 39711575Full record

ArticleResearch square2024

The impact of chronic intermittent hypoxia on enzymatic activity in memory-associated brain regions of male and female rats.

Steve Mabry, Jessica L Bradshaw, Jennifer J Gardner, E Nicole Wilson, Janak Sunuwar, Hannah Yeung, Sharad Shrestha, J Thomas Cunningham, Rebecca L Cunningham

Abstract readPreprint
In one paragraph

Article in Research square, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Steve MabryUniversity of North Texas Health Science Center.
Jessica L BradshawUniversity of North Texas Health Science Center.
Jennifer J GardnerUniversity of North Texas Health Science Center.
E Nicole WilsonUniversity of North Texas Health Science Center.
Janak SunuwarUniversity of North Texas Health Science Center.
Hannah YeungUniversity of North Texas Health Science Center.
Sharad ShresthaUniversity of North Texas Health Science Center.
J Thomas CunninghamUniversity of North Texas Health Science Center.
Rebecca L CunninghamUniversity of North Texas Health Science Center.

Funding

Intermittent hypoxia and hypertension: Role of the lamina terminalisR01HL155977 · NHLBI · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI George Edward Farmer · 2022 to 2024
$2.0M
Training in the Neurobiology of Aging and Alzheimer's DiseaseT32AG020494 · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · 2002 to 2025
$927k
The Impact of Sex and Hippocampal Angiotensin II on Alzheimer's DiseaseR01AG085296 · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · 2025 to 2025
$715k
NHLBI NIH HHS R01 HL155977NIA NIH HHS R01 AG085296NIA NIH HHS T32 AG020494NINDS NIH HHS R01 NS091359
6 · The paper itself

Abstract

Background: Obstructive 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 as 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) and neuronal activation (early growth response protein 1, EGR-1) in brain regions associated with learning and memory. We used a rat model of OSA known as chronic intermittent hypoxia (CIH) to investigate protease activity (calpain and caspase-3) and neuronal activation (early growth response protein 1, EGR-1) in brain regions associated with learning and memory. Methods: Male 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. Results: CIH 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. Conclusions: Overall, these data show that 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.

Indexed as

calpaincaspase-3chronic intermittent hypoxiaearly growth response protein 1sex differences

Identifiers

PMID39711575
PMCPMC11661378

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.