Sex-Related Microglial Perturbation Is Related to Mitochondrial Changes in a Model of Alzheimer’s Disease
Many studies implicate microglia in the pathogenesis of Alzheimer’s disease (AD) but precisely how these cells make their impact has not been determined to date. One contributory factor is likely to be the enhanced production of inflammatory mediators and it is now known that microglia with this sec...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-07-01
|
| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2022.939830/full |
| _version_ | 1811291257829326848 |
|---|---|
| author | Eoin O’Neill Virginia Mela Aline Sayd Gaban Sibylle Bechet Aoife McGrath Aife Walsh Allison McIntosh Marina A. Lynch |
| author_facet | Eoin O’Neill Virginia Mela Aline Sayd Gaban Sibylle Bechet Aoife McGrath Aife Walsh Allison McIntosh Marina A. Lynch |
| author_sort | Eoin O’Neill |
| collection | DOAJ |
| description | Many studies implicate microglia in the pathogenesis of Alzheimer’s disease (AD) but precisely how these cells make their impact has not been determined to date. One contributory factor is likely to be the enhanced production of inflammatory mediators and it is now known that microglia with this secretory phenotype exhibit other adaptations including in their morphology, function, and metabolism. AD, like many neurological disorders, demonstrates a sex bias and recent evidence indicates that the sexual dimorphism in microglial function, which has been recognized for many years in early development, persists into adulthood and aging. Here, we demonstrate sex-related differences in microglia from post mortem tissue of male and female AD patients and a marked increase in the number of dystrophic and rod-shaped microglia in tissue from female AD patients compared with males. Furthermore, there was an increase in iron-laden microglia in tissue from female AD patients and this has been reported to reflect mitochondrial changes. To address this further, we assessed changes in microglia from male and female APP/PS1 mice and demonstrate that iron accumulation in microglia is increased to a greater extent in tissue prepared from females compared with males. This was associated with altered expression of genes coding for proteins that modulate mitochondrial function. The findings suggest that sex-related differences in the severity and perhaps incidence of AD may, at least in part, arise from sexual dimorphism in microglia. |
| first_indexed | 2024-04-13T04:26:45Z |
| format | Article |
| id | doaj.art-52af470307374b01b1ed061ed44c1e18 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-13T04:26:45Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-52af470307374b01b1ed061ed44c1e182022-12-22T03:02:30ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022022-07-011610.3389/fncel.2022.939830939830Sex-Related Microglial Perturbation Is Related to Mitochondrial Changes in a Model of Alzheimer’s DiseaseEoin O’NeillVirginia MelaAline Sayd GabanSibylle BechetAoife McGrathAife WalshAllison McIntoshMarina A. LynchMany studies implicate microglia in the pathogenesis of Alzheimer’s disease (AD) but precisely how these cells make their impact has not been determined to date. One contributory factor is likely to be the enhanced production of inflammatory mediators and it is now known that microglia with this secretory phenotype exhibit other adaptations including in their morphology, function, and metabolism. AD, like many neurological disorders, demonstrates a sex bias and recent evidence indicates that the sexual dimorphism in microglial function, which has been recognized for many years in early development, persists into adulthood and aging. Here, we demonstrate sex-related differences in microglia from post mortem tissue of male and female AD patients and a marked increase in the number of dystrophic and rod-shaped microglia in tissue from female AD patients compared with males. Furthermore, there was an increase in iron-laden microglia in tissue from female AD patients and this has been reported to reflect mitochondrial changes. To address this further, we assessed changes in microglia from male and female APP/PS1 mice and demonstrate that iron accumulation in microglia is increased to a greater extent in tissue prepared from females compared with males. This was associated with altered expression of genes coding for proteins that modulate mitochondrial function. The findings suggest that sex-related differences in the severity and perhaps incidence of AD may, at least in part, arise from sexual dimorphism in microglia.https://www.frontiersin.org/articles/10.3389/fncel.2022.939830/fullAlzheimer’s diseasemicrogliamitochondrial dysfunctioniron accumulationsex-related differences |
| spellingShingle | Eoin O’Neill Virginia Mela Aline Sayd Gaban Sibylle Bechet Aoife McGrath Aife Walsh Allison McIntosh Marina A. Lynch Sex-Related Microglial Perturbation Is Related to Mitochondrial Changes in a Model of Alzheimer’s Disease Frontiers in Cellular Neuroscience Alzheimer’s disease microglia mitochondrial dysfunction iron accumulation sex-related differences |
| title | Sex-Related Microglial Perturbation Is Related to Mitochondrial Changes in a Model of Alzheimer’s Disease |
| title_full | Sex-Related Microglial Perturbation Is Related to Mitochondrial Changes in a Model of Alzheimer’s Disease |
| title_fullStr | Sex-Related Microglial Perturbation Is Related to Mitochondrial Changes in a Model of Alzheimer’s Disease |
| title_full_unstemmed | Sex-Related Microglial Perturbation Is Related to Mitochondrial Changes in a Model of Alzheimer’s Disease |
| title_short | Sex-Related Microglial Perturbation Is Related to Mitochondrial Changes in a Model of Alzheimer’s Disease |
| title_sort | sex related microglial perturbation is related to mitochondrial changes in a model of alzheimer s disease |
| topic | Alzheimer’s disease microglia mitochondrial dysfunction iron accumulation sex-related differences |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2022.939830/full |
| work_keys_str_mv | AT eoinoneill sexrelatedmicroglialperturbationisrelatedtomitochondrialchangesinamodelofalzheimersdisease AT virginiamela sexrelatedmicroglialperturbationisrelatedtomitochondrialchangesinamodelofalzheimersdisease AT alinesaydgaban sexrelatedmicroglialperturbationisrelatedtomitochondrialchangesinamodelofalzheimersdisease AT sibyllebechet sexrelatedmicroglialperturbationisrelatedtomitochondrialchangesinamodelofalzheimersdisease AT aoifemcgrath sexrelatedmicroglialperturbationisrelatedtomitochondrialchangesinamodelofalzheimersdisease AT aifewalsh sexrelatedmicroglialperturbationisrelatedtomitochondrialchangesinamodelofalzheimersdisease AT allisonmcintosh sexrelatedmicroglialperturbationisrelatedtomitochondrialchangesinamodelofalzheimersdisease AT marinaalynch sexrelatedmicroglialperturbationisrelatedtomitochondrialchangesinamodelofalzheimersdisease |