Loss of sex hormones alters indices of prefrontal cortex and hippocampal insulin signaling and increases lipid content in a region‐specific manner independent of cardiac pressure overload in female aortic‐banded Yucatan miniature swine
Bibliographic record
Abstract
Estimates indicate ~50% of patients with heart failure with preserved ejection fraction (HFpEF) experience dementia. Interestingly, postmenopausal women represent the largest cohort of patients with HFpEF. Impaired insulin signaling in the brain has been implicated in dementia, and may be related to regional changes in the neuronal lipid composition. How such processes are effected by the loss of female sex hormones remains to be elucidated. Using a translationally relevant large animal model of pressure overload‐induced heart failure, we tested the hypotheses that the loss of female sex hormones alters proteins involved in brain insulin signaling, and that such changes are associated with an altered lipid profile. Twenty‐eight female Yucatan miniature swine were divided into four groups (n=7): control (CON), aortic banding (AB; pressure overload model of heart failure), ovariectomy (OVX), and AB with OVX (AB‐OVX). Pigs underwent OVX and AB at 7 and 8 months of age, respectively, and prefrontal cortex and hippocampus tissues were collected at 14 months. Estrogen receptor‐α (p<0.05) content was reduced with OVX in both cortical and hippocampal brain regions. In the cortex, OVX reduced total Akt (p<0.05) and synaptophysin (p<0.10), and in the hippocampus OVX reduced phospho‐Akt Ser473 (p<0.05) and phospho‐ERK (p<0.05). Neuronal lipid composition in the prefrontal cortex and hippocampus revealed increases in total lipids (p<0.10), saturated (p<0.10), and monounsaturated fatty acids (p<0.05) with OVX. The hippocampus had increased total (p<0.10), monounsaturated (p<0.05), and polyunsaturated fats (p<0.10). No changes were observed in OVX for polyunsaturated fats. In conclusion, the loss of female sex hormones alters Akt and MAPK/ERK protein content/pathway activation predominantly in the hippocampus, independent of cardiac pressure overload. Impaired indices of hippocampal insulin signaling were associated with a local accumulation of saturated and monounsaturated fats. Overall, the loss of female sex hormones may contribute to the development of dementia in a translational swine model of pressure overload HF with potential relevance to human HFpEF through metabolic pathways influencing cognition. Support or Funding Information NIH R01 HL112998, PI: CAE American Heart Association #16POST2776005, PI: TDO Alzheimer Society of Brant, Haldimand, Norfolk, Hamilton, and Halton, PI: REKM This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".