Females exhibit higher GluA2 levels and outperform males in active place avoidance despite increased amyloid plaques in TgF344-Alzheimer’s rats
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-23801-w |
| _version_ | 1798018382624194560 |
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| author | Osama Chaudry Kelechi Ndukwe Lei Xie Maria Figueiredo-Pereira Peter Serrano Patricia Rockwell |
| author_facet | Osama Chaudry Kelechi Ndukwe Lei Xie Maria Figueiredo-Pereira Peter Serrano Patricia Rockwell |
| author_sort | Osama Chaudry |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T16:23:02Z |
| format | Article |
| id | doaj.art-362429dd53ff4821afb36ff0d130ef5c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T16:23:02Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-362429dd53ff4821afb36ff0d130ef5c2022-12-22T04:14:16ZengNature PortfolioScientific Reports2045-23222022-11-0112111510.1038/s41598-022-23801-wFemales exhibit higher GluA2 levels and outperform males in active place avoidance despite increased amyloid plaques in TgF344-Alzheimer’s ratsOsama Chaudry0Kelechi Ndukwe1Lei Xie2Maria Figueiredo-Pereira3Peter Serrano4Patricia Rockwell5Department of Biological Sciences, Hunter College CUNYDepartment of Biological Sciences, Hunter College CUNYDepartment of Computer Sciences, Hunter College CUNYDepartment of Biological Sciences, Hunter College CUNYDepartment of Psychology, Hunter College CUNYDepartment of Biological Sciences, Hunter College CUNYAbstract 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.https://doi.org/10.1038/s41598-022-23801-w |
| spellingShingle | Osama Chaudry Kelechi Ndukwe Lei Xie Maria Figueiredo-Pereira Peter Serrano Patricia Rockwell Females exhibit higher GluA2 levels and outperform males in active place avoidance despite increased amyloid plaques in TgF344-Alzheimer’s rats Scientific Reports |
| title | Females exhibit higher GluA2 levels and outperform males in active place avoidance despite increased amyloid plaques in TgF344-Alzheimer’s rats |
| title_full | Females exhibit higher GluA2 levels and outperform males in active place avoidance despite increased amyloid plaques in TgF344-Alzheimer’s rats |
| title_fullStr | Females exhibit higher GluA2 levels and outperform males in active place avoidance despite increased amyloid plaques in TgF344-Alzheimer’s rats |
| title_full_unstemmed | Females exhibit higher GluA2 levels and outperform males in active place avoidance despite increased amyloid plaques in TgF344-Alzheimer’s rats |
| title_short | Females exhibit higher GluA2 levels and outperform males in active place avoidance despite increased amyloid plaques in TgF344-Alzheimer’s rats |
| title_sort | females exhibit higher glua2 levels and outperform males in active place avoidance despite increased amyloid plaques in tgf344 alzheimer s rats |
| url | https://doi.org/10.1038/s41598-022-23801-w |
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