P3‐408: TARGETING GLYCEROPHOSPHOLIPIDOME TO IMPROVE LEARNING AND MEMORY IN THE TGCRND8 AD MOUSE MODEL
Bibliographic record
Abstract
The human brain is enriched in omega series unsaturated fatty acids (FAs) whose deficiencies have been linked to a variety of neurological disorders including AD. Intriguingly, AD patients have reduced levels of ω-3 and ω-6/9 FAs compared with age-matched non-demented controls. More importantly, their levels were shown to correlate with severity of mild cognitive impairment (MCI) and dementia. These observations have prompted us to investigate whether dietary supplementation of the omega series FAs may restore their normal levels and thus improve learning and memory in the TgCRND8 AD mouse model. TgCRND8 mice and their NonTg littermates received ω-3 or ω-6/9 FAs (75mg/Kg/day) supplementation for 4 months starting at 2 months of age. Mice received vehicle were used as “untreated” controls. The glycerophosphocholine (PC) lipidome was profiled in the hippocampus, temporal cortex, and plasma in these mice following assessment of learning and memory in the Morris Water Maze (MWM). PCs were extracted using a modified Bligh & Dyer method and profiling was performed by LC-ESI-MS. TgCRND8 mice displayed learning and memory impairment compared to NonTg littermates. We further showed that the TgCRND8 mice used a less effective search strategy than NonTg littermates in the MWM test. There were 24 PC species whose abundance was significantly altered in the TgCRND8 mice. Significant correlations between the abundance of 13 species in either the hippocampus or temporal cortex were detected that could be predicted by associated changes in circulating lipidome. While supplementation with ω-3 FA did not improve learning and memory of the transgenic mice, supplementation with ω-6/-9 FAs significantly improved their performance in the MWM test due at least in part to adoption of a more effective searching strategy. Overall, dietary supplementation of FAs appeared to have more profound effects on plasma PC lipidome than genotype did as revealed by cluster analysis. Importantly, the abundance of six plasma PC species was significantly correlated with individual learning and memory. These data provide proof of principle that the central and circulating lipidome can be modulated to improve learning and memory.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".