Early Onset of Sex-Dependent Mitochondrial Deficits in the Cortex of 3xTg Alzheimer’s Mice
Alzheimer’s disease (AD) is a major public health concern worldwide. Advanced age and female sex are two of the most prominent risk factors for AD. AD is characterized by progressive neuronal loss, especially in the cortex and hippocampus, and mitochondrial dysfunction has been proposed to be an ear...
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MDPI AG
2020-06-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/6/1541 |
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| author | Jelena Djordjevic Subir Roy Chowdhury Wanda M. Snow Claudia Perez Chris Cadonic Paul Fernyhough Benedict C. Albensi |
| author_facet | Jelena Djordjevic Subir Roy Chowdhury Wanda M. Snow Claudia Perez Chris Cadonic Paul Fernyhough Benedict C. Albensi |
| author_sort | Jelena Djordjevic |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a major public health concern worldwide. Advanced age and female sex are two of the most prominent risk factors for AD. AD is characterized by progressive neuronal loss, especially in the cortex and hippocampus, and mitochondrial dysfunction has been proposed to be an early event in the onset and progression of the disease. Our results showed early perturbations in mitochondrial function in 3xTg mouse brain, with the cortex being more susceptible to mitochondrial changes than the hippocampus. In the cortex of 3xTg females, decreased coupled and uncoupled respiration were evident early (at 2 months of age), while in males it appeared later at 6 months of age. We observed increased coupled respiration in the hippocampus of 2-month-old 3xTg females, but no changes were detected later in life. Changes in mitochondrial dynamics were indicated by decreased mitofusin (Mfn2) and increased dynamin related protein 1 (Drp1) (only in females) in the hippocampus and cortex of 3xTg mice. Our findings highlight the importance of controlling and accounting for sex, brain region, and age in studies examining brain bioenergetics using this common AD model in order to more accurately evaluate potential therapies and improve the sex-specific translatability of preclinical findings. |
| first_indexed | 2024-03-10T18:54:12Z |
| format | Article |
| id | doaj.art-5487f814edcf4b9c853e00ac821bab16 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T18:54:12Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-5487f814edcf4b9c853e00ac821bab162023-11-20T04:52:27ZengMDPI AGCells2073-44092020-06-0196154110.3390/cells9061541Early Onset of Sex-Dependent Mitochondrial Deficits in the Cortex of 3xTg Alzheimer’s MiceJelena Djordjevic0Subir Roy Chowdhury1Wanda M. Snow2Claudia Perez3Chris Cadonic4Paul Fernyhough5Benedict C. Albensi6Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H2A6, CanadaDivision of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H2A6, CanadaDivision of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H2A6, CanadaDivision of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H2A6, CanadaDivision of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H2A6, CanadaDivision of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H2A6, CanadaDivision of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H2A6, CanadaAlzheimer’s disease (AD) is a major public health concern worldwide. Advanced age and female sex are two of the most prominent risk factors for AD. AD is characterized by progressive neuronal loss, especially in the cortex and hippocampus, and mitochondrial dysfunction has been proposed to be an early event in the onset and progression of the disease. Our results showed early perturbations in mitochondrial function in 3xTg mouse brain, with the cortex being more susceptible to mitochondrial changes than the hippocampus. In the cortex of 3xTg females, decreased coupled and uncoupled respiration were evident early (at 2 months of age), while in males it appeared later at 6 months of age. We observed increased coupled respiration in the hippocampus of 2-month-old 3xTg females, but no changes were detected later in life. Changes in mitochondrial dynamics were indicated by decreased mitofusin (Mfn2) and increased dynamin related protein 1 (Drp1) (only in females) in the hippocampus and cortex of 3xTg mice. Our findings highlight the importance of controlling and accounting for sex, brain region, and age in studies examining brain bioenergetics using this common AD model in order to more accurately evaluate potential therapies and improve the sex-specific translatability of preclinical findings.https://www.mdpi.com/2073-4409/9/6/1541Alzheimer’s disease3xTgmitochondriacortexhippocampus |
| spellingShingle | Jelena Djordjevic Subir Roy Chowdhury Wanda M. Snow Claudia Perez Chris Cadonic Paul Fernyhough Benedict C. Albensi Early Onset of Sex-Dependent Mitochondrial Deficits in the Cortex of 3xTg Alzheimer’s Mice Cells Alzheimer’s disease 3xTg mitochondria cortex hippocampus |
| title | Early Onset of Sex-Dependent Mitochondrial Deficits in the Cortex of 3xTg Alzheimer’s Mice |
| title_full | Early Onset of Sex-Dependent Mitochondrial Deficits in the Cortex of 3xTg Alzheimer’s Mice |
| title_fullStr | Early Onset of Sex-Dependent Mitochondrial Deficits in the Cortex of 3xTg Alzheimer’s Mice |
| title_full_unstemmed | Early Onset of Sex-Dependent Mitochondrial Deficits in the Cortex of 3xTg Alzheimer’s Mice |
| title_short | Early Onset of Sex-Dependent Mitochondrial Deficits in the Cortex of 3xTg Alzheimer’s Mice |
| title_sort | early onset of sex dependent mitochondrial deficits in the cortex of 3xtg alzheimer s mice |
| topic | Alzheimer’s disease 3xTg mitochondria cortex hippocampus |
| url | https://www.mdpi.com/2073-4409/9/6/1541 |
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