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Cited by 28Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroscience and Neuropharmacology Research

Females exhibit higher GluA2 levels and outperform males in active place avoidance despite increased amyloid plaques in TgF344-Alzheimer's rats

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Chaudry, Osama, Ndukwe, Kelechi, Xie, Lei, Figueiredo-Pereira, Maria, Serrano, Peter, Rockwell, Patricia·2022·Scientific Reports
DOI 10.1038/s41598-022-23801-wPMC PMC9646806
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Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is most prevalent in females. While estrogen provides neuroprotection in females, sex mediated differences in the development of AD pathology are not fully elucidated. Therefore, comparing events between sexes in early-stage AD pathology may reveal more effective therapeutic targets of intervention. To address sex differences, we analyzed early-stage 9-month male and female TgF344-AD (Tg-AD) rats, an AD model carrying the APPswe and Presenilin 1 (PS1ΔE9) mutations that develops progressive age-dependent AD pathology similar to humans. Tg-AD females significantly outperformed Tg-AD males in the active place avoidance (aPAT) test that assesses hippocampal-dependent spatial learning and memory. However, comparisons between Tg-AD male or female rats and their WT counterparts showed significant deficits for female but not male rats. Nevertheless, Tg-AD females experienced significantly less hippocampal neuronal loss with higher GluA2 subunit levels than Tg-AD males. Unexpectedly, Tg-AD females displayed higher levels of hippocampal amyloid plaques than Tg-AD males. Thus, we propose that GluA2 may provide a neuroprotective function for Tg-AD females in our rat model by mitigating cognitive impairment independently of amyloid plaques. Elucidating this protective mechanism in AD could lead to new targets for early intervention.

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  • Active avoidance tests are particularly valuable for evaluating hippocampal-dependent cognitive functions.

    “Active avoidance tests are particularly valuable for evaluating hippocampal-dependent cognitive functions (Anagnostaras et al., 2010; Chaudry et al., 2022; Kajs et al., 2022).”

    From Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model (2024) · cites this paper as Chaudry et al., 2022

  • Previous studies demonstrate that in animal models of neurodegenerative disorders, such as AD, cognitive function and learning and memory are significantly impaired.

    “Previous studies demonstrate that in animal models of neurodegenerative disorders, such as AD, cognitive function and learning and memory are significantly impaired (Anagnostaras et al., 2010; Chaudry et al., 2022; Kajs et al., 2022; Webster et al., 2014) and that VEEV infections can have an adverse effect on learning memory (Dave and Klein, 2023; Ronca et al., 2016).”

    From Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model (2024) · cites this paper as Chaudry et al., 2022

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Authors
Chaudry, O., Ndukwe, K., Xie, L., Figueiredo-Pereira, M., Serrano, P., & Rockwell, P.
Affiliations
  • Hunter College (US)
  • The Graduate Center, CUNY (US)
Corresponding author
Rockwell, Patricia
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2022-11-09
Volume
12
Issue
1
Pages
19129-19129
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-022-23801-w
PMC
PMC9646806
OpenAlex
W4308627355
Cited by
28
References
68
Citations by year
2026: 5 · 2025: 13 · 2024: 8 · 2023: 2
FWCI
3.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • CUNY Academic Works (City University of New York) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institutes of Health (training grant R25GM060665, NIH/NIA R01AG057555)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
Alzheimer's disease, sex differences, GluR2 subunit, spatial learning and memory, amyloid plaques, hippocampal neuronal loss, TgF344-AD rats, APPswe, neuroprotection, estrogen
MeSH terms
Alzheimer Disease, Animals, Disease Models, Animal, Female, Humans, Male, Mice, Transgenic, Rats, Inbred F344, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Neurodegenerative Diseases, Mice, Rats, Presenilin-1, Rats, Transgenic, Plaque, Amyloid

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