{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:13:32Z","timestamp":1791821612606,"version":"4.3.4"},"reference-count":73,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T00:00:00Z","timestamp":1592956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-162144"],"award-info":[{"award-number":["PJT-162144"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"St. Boniface Hospital Research Foundation","award":["1406-3216"],"award-info":[{"award-number":["1406-3216"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Alzheimer\u2019s 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.<\/jats:p>","DOI":"10.3390\/cells9061541","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T10:54:59Z","timestamp":1592996099000},"page":"1541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Early Onset of Sex-Dependent Mitochondrial Deficits in the Cortex of 3xTg Alzheimer\u2019s Mice"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9769-6857","authenticated-orcid":false,"given":"Jelena","family":"Djordjevic","sequence":"first","affiliation":[{"name":"Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H2A6, Canada"},{"name":"Department of Pharmacology &amp; Therapeutics, University of Manitoba, Winnipeg, MB R2H2A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subir","family":"Roy Chowdhury","sequence":"additional","affiliation":[{"name":"Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H2A6, Canada"},{"name":"Research Institute in Oncology, CancerCare Manitoba, University of Manitoba, Winnipeg, MB R2H2A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanda M.","family":"Snow","sequence":"additional","affiliation":[{"name":"Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H2A6, Canada"},{"name":"Department of Pharmacology &amp; Therapeutics, University of Manitoba, Winnipeg, MB R2H2A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Perez","sequence":"additional","affiliation":[{"name":"Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H2A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Cadonic","sequence":"additional","affiliation":[{"name":"Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H2A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Fernyhough","sequence":"additional","affiliation":[{"name":"Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H2A6, Canada"},{"name":"Department of Pharmacology &amp; Therapeutics, University of Manitoba, Winnipeg, MB R2H2A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedict C.","family":"Albensi","sequence":"additional","affiliation":[{"name":"Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H2A6, Canada"},{"name":"Department of Pharmacology &amp; Therapeutics, University of Manitoba, Winnipeg, MB R2H2A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/j.jalz.2016.08.004","article-title":"Sex biology contributions to vulnerability to Alzheimer\u2019s disease: A think tank convened by the Women\u2019s Alzheimer\u2019s Research Initiative","volume":"12","author":"Snyder","year":"2016","journal-title":"Alzheimers Dement."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"437","DOI":"10.31887\/DCNS.2016.18.4\/cepperson","article-title":"Considering sex and gender in Alzheimer disease and other dementias","volume":"18","author":"Podcasy","year":"2016","journal-title":"Dialogues Clin. 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