Age- and sex-associated alterations in hypothalamic mitochondrial bioenergetics and inflammatory-associated signaling in the 3xTg mouse model of Alzheimer’s disease
Bibliographic record
Abstract
Mitochondrial dysfunction and associated inflammatory signaling are pivotal in both aging and in Alzheimer's disease (AD). Studies have also shown that hypothalamic function is affected in AD. The hypothalamus may be a target for AD drugs given that mitochondrial alterations are observed in the hypothalamus. This study investigated how age and sex affect mitochondrial bioenergetics and inflammatory signaling in the hypothalamic mitochondria of 3xTg and control mice at 2, 6, and 13 months, aiming to enhance our understanding of these processes in aging and AD. Parameters included oxygen consumption rates, expression levels of subunits comprising mitochondrial complexes I-V, the enzymatic activity of cytochrome c oxidase (COX), transcription factors associated with inflammation such as NF-κB, pIκB-α, Nrf2, and other inflammatory biomarkers. Hypothalamic mitochondrial dysfunction was observed in 3xTg females as early as 2 months, but no changes were detected in 3xTg males until 6 months of age. In 3xTg mice, subunit expression levels for mitochondrial complexes I-II were significantly reduced in both sexes. Significant sex-based differences in COX activity were also observed at 13 months of age, with levels being lower in females compared to males. In addition, significant sex differences were indicated in NF-κB, pIκB-α, Nrf2, and other inflammatory biomarkers at different age groups during normal aging and AD progression. These findings highlight important sex differences in hypothalamic bioenergetics and inflammation, offering insights into potential new targets for preventing and/or treating AD.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".