Potential Alzheimer’s early biomarkers in a transgenic rat model and benefits of diazoxide/dibenzoylmethane co-treatment on spatial memory and AD-pathology
Abstract Alzheimer’s disease (AD) is the major form of dementia prevalent in older adults and with a high incidence in females. Identification of early biomarkers is essential for preventive intervention to delay its progression. Furthermore, due to its multifactorial nature, a multi-target approach...
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Nature Portfolio
2024-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-54156-z |
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| author | Charles H. Wallace Giovanni Oliveros Lei Xie Peter Serrano Patricia Rockwell Maria Figueiredo-Pereira |
| author_facet | Charles H. Wallace Giovanni Oliveros Lei Xie Peter Serrano Patricia Rockwell Maria Figueiredo-Pereira |
| author_sort | Charles H. Wallace |
| collection | DOAJ |
| description | Abstract Alzheimer’s disease (AD) is the major form of dementia prevalent in older adults and with a high incidence in females. Identification of early biomarkers is essential for preventive intervention to delay its progression. Furthermore, due to its multifactorial nature, a multi-target approach could be therapeutically beneficial. Our studies included 4- (pre-pathology) and 11-month (mild-pathology) TgF344-AD rats, a transgenic Alzheimer’s model that exhibits age-dependent AD progression. We identified two potential early biomarker genes for AD, early growth response 2 (EGR2) and histone 1H2AA (HIST1H2AA), in the hippocampus of 4-month females. Out of 17,168 genes analyzed by RNA sequencing, expression of these two genes was significantly altered in 4-month TgF344-AD rats compared to wild-type littermates. We also evaluated co-treatment with diazoxide (DZ), a potassium channel activator, and dibenzoylmethane (DIB), which inhibits eIF2α-P activity, on TgF344-AD and wild-type rats. DZ/DIB-treatment mitigated spatial memory deficits and buildup of hippocampal Aβ plaques and tau PHF in 11-month TgF344-AD rats but had no effect on wild-type littermates. To our knowledge, this preclinical study is the first to report EGR2 and HIST1H2AA as potential AD biomarkers in females, and the benefits of DZ/DIB-treatment in AD. Evaluations across multiple AD-related models is warranted to corroborate our findings. |
| first_indexed | 2024-03-07T15:09:41Z |
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| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:09:41Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj.art-f53658ccfa664502aadb3542cf8eca212024-03-05T18:45:19ZengNature PortfolioScientific Reports2045-23222024-02-0114111310.1038/s41598-024-54156-zPotential Alzheimer’s early biomarkers in a transgenic rat model and benefits of diazoxide/dibenzoylmethane co-treatment on spatial memory and AD-pathologyCharles H. Wallace0Giovanni Oliveros1Lei Xie2Peter Serrano3Patricia Rockwell4Maria Figueiredo-Pereira5Department of Biological Sciences, Hunter College CUNY and Graduate CenterDepartment of Biological Sciences, Hunter College CUNY and Graduate CenterDepartment of Computer Sciences, Hunter College CUNYDepartment of Psychology, Hunter College CUNYDepartment of Biological Sciences, Hunter College CUNY and Graduate CenterDepartment of Biological Sciences, Hunter College CUNY and Graduate CenterAbstract Alzheimer’s disease (AD) is the major form of dementia prevalent in older adults and with a high incidence in females. Identification of early biomarkers is essential for preventive intervention to delay its progression. Furthermore, due to its multifactorial nature, a multi-target approach could be therapeutically beneficial. Our studies included 4- (pre-pathology) and 11-month (mild-pathology) TgF344-AD rats, a transgenic Alzheimer’s model that exhibits age-dependent AD progression. We identified two potential early biomarker genes for AD, early growth response 2 (EGR2) and histone 1H2AA (HIST1H2AA), in the hippocampus of 4-month females. Out of 17,168 genes analyzed by RNA sequencing, expression of these two genes was significantly altered in 4-month TgF344-AD rats compared to wild-type littermates. We also evaluated co-treatment with diazoxide (DZ), a potassium channel activator, and dibenzoylmethane (DIB), which inhibits eIF2α-P activity, on TgF344-AD and wild-type rats. DZ/DIB-treatment mitigated spatial memory deficits and buildup of hippocampal Aβ plaques and tau PHF in 11-month TgF344-AD rats but had no effect on wild-type littermates. To our knowledge, this preclinical study is the first to report EGR2 and HIST1H2AA as potential AD biomarkers in females, and the benefits of DZ/DIB-treatment in AD. Evaluations across multiple AD-related models is warranted to corroborate our findings.https://doi.org/10.1038/s41598-024-54156-zPolypharmacologyDrug repurposingAlzheimer’sPotassium channel activatoreIF2α activatorEGR2 |
| spellingShingle | Charles H. Wallace Giovanni Oliveros Lei Xie Peter Serrano Patricia Rockwell Maria Figueiredo-Pereira Potential Alzheimer’s early biomarkers in a transgenic rat model and benefits of diazoxide/dibenzoylmethane co-treatment on spatial memory and AD-pathology Scientific Reports Polypharmacology Drug repurposing Alzheimer’s Potassium channel activator eIF2α activator EGR2 |
| title | Potential Alzheimer’s early biomarkers in a transgenic rat model and benefits of diazoxide/dibenzoylmethane co-treatment on spatial memory and AD-pathology |
| title_full | Potential Alzheimer’s early biomarkers in a transgenic rat model and benefits of diazoxide/dibenzoylmethane co-treatment on spatial memory and AD-pathology |
| title_fullStr | Potential Alzheimer’s early biomarkers in a transgenic rat model and benefits of diazoxide/dibenzoylmethane co-treatment on spatial memory and AD-pathology |
| title_full_unstemmed | Potential Alzheimer’s early biomarkers in a transgenic rat model and benefits of diazoxide/dibenzoylmethane co-treatment on spatial memory and AD-pathology |
| title_short | Potential Alzheimer’s early biomarkers in a transgenic rat model and benefits of diazoxide/dibenzoylmethane co-treatment on spatial memory and AD-pathology |
| title_sort | potential alzheimer s early biomarkers in a transgenic rat model and benefits of diazoxide dibenzoylmethane co treatment on spatial memory and ad pathology |
| topic | Polypharmacology Drug repurposing Alzheimer’s Potassium channel activator eIF2α activator EGR2 |
| url | https://doi.org/10.1038/s41598-024-54156-z |
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