Low-Dose Chidamide Treatment Displays Sex-Specific Differences in the 3xTg-AD Mouse
Epigenetic compounds have become attractive small molecules for targeting the multifaceted aspects of Alzheimer’s disease (AD). Although AD disproportionately affects women, most of the current literature investigating epigenetic compounds for the treatment of AD do not report sex-specific results....
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/9/1324 |
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| author | Jessica Dennison Armando Mendez Angela Szeto Ines Lohse Claes Wahlestedt Claude-Henry Volmar |
| author_facet | Jessica Dennison Armando Mendez Angela Szeto Ines Lohse Claes Wahlestedt Claude-Henry Volmar |
| author_sort | Jessica Dennison |
| collection | DOAJ |
| description | Epigenetic compounds have become attractive small molecules for targeting the multifaceted aspects of Alzheimer’s disease (AD). Although AD disproportionately affects women, most of the current literature investigating epigenetic compounds for the treatment of AD do not report sex-specific results. This is remarkable because there is rising evidence that epigenetic compounds intrinsically affect males and females differently. This manuscript explores the sexual dimorphism observed after chronic, low-dose administration of a clinically relevant histone deacetylase inhibitor, chidamide (Tucidinostat), in the 3xTg-AD mouse model. We found that chidamide treatment significantly improves glucose tolerance and increases expression of glucose transporters in the brain of males. We also report a decrease in total tau in chidamide-treated mice. Differentially expressed genes in chidamide-treated mice were much greater in males than females. Genes involved in the neuroinflammatory pathway and amyloid processing pathway were mostly upregulated in chidamide-treated males while downregulated in chidamide-treated females. This work highlights the need for drug discovery projects to consider sex as a biological variable to facilitate translation. |
| first_indexed | 2024-03-10T22:59:49Z |
| format | Article |
| id | doaj.art-e6eb94147a5649e6876caa0e49838f42 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T22:59:49Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-e6eb94147a5649e6876caa0e49838f422023-11-19T09:45:23ZengMDPI AGBiomolecules2218-273X2023-08-01139132410.3390/biom13091324Low-Dose Chidamide Treatment Displays Sex-Specific Differences in the 3xTg-AD MouseJessica Dennison0Armando Mendez1Angela Szeto2Ines Lohse3Claes Wahlestedt4Claude-Henry Volmar5Department of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USADiabetes Research Institute, Division of Endocrinology, Diabetes, and Metabolism, University of Miami Miller School of Medicine, Miami, FL 33136, USADiabetes Research Institute, Division of Endocrinology, Diabetes, and Metabolism, University of Miami Miller School of Medicine, Miami, FL 33136, USADepartment of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USADepartment of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USADepartment of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USAEpigenetic compounds have become attractive small molecules for targeting the multifaceted aspects of Alzheimer’s disease (AD). Although AD disproportionately affects women, most of the current literature investigating epigenetic compounds for the treatment of AD do not report sex-specific results. This is remarkable because there is rising evidence that epigenetic compounds intrinsically affect males and females differently. This manuscript explores the sexual dimorphism observed after chronic, low-dose administration of a clinically relevant histone deacetylase inhibitor, chidamide (Tucidinostat), in the 3xTg-AD mouse model. We found that chidamide treatment significantly improves glucose tolerance and increases expression of glucose transporters in the brain of males. We also report a decrease in total tau in chidamide-treated mice. Differentially expressed genes in chidamide-treated mice were much greater in males than females. Genes involved in the neuroinflammatory pathway and amyloid processing pathway were mostly upregulated in chidamide-treated males while downregulated in chidamide-treated females. This work highlights the need for drug discovery projects to consider sex as a biological variable to facilitate translation.https://www.mdpi.com/2218-273X/13/9/1324Alzheimer’sepigeneticsHDAC inhibitorsex differences3xTg-AD mouse |
| spellingShingle | Jessica Dennison Armando Mendez Angela Szeto Ines Lohse Claes Wahlestedt Claude-Henry Volmar Low-Dose Chidamide Treatment Displays Sex-Specific Differences in the 3xTg-AD Mouse Biomolecules Alzheimer’s epigenetics HDAC inhibitor sex differences 3xTg-AD mouse |
| title | Low-Dose Chidamide Treatment Displays Sex-Specific Differences in the 3xTg-AD Mouse |
| title_full | Low-Dose Chidamide Treatment Displays Sex-Specific Differences in the 3xTg-AD Mouse |
| title_fullStr | Low-Dose Chidamide Treatment Displays Sex-Specific Differences in the 3xTg-AD Mouse |
| title_full_unstemmed | Low-Dose Chidamide Treatment Displays Sex-Specific Differences in the 3xTg-AD Mouse |
| title_short | Low-Dose Chidamide Treatment Displays Sex-Specific Differences in the 3xTg-AD Mouse |
| title_sort | low dose chidamide treatment displays sex specific differences in the 3xtg ad mouse |
| topic | Alzheimer’s epigenetics HDAC inhibitor sex differences 3xTg-AD mouse |
| url | https://www.mdpi.com/2218-273X/13/9/1324 |
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