A14 THE INTESTINAL MICROBIOTA CONTRIBUTES TO AGE-RELATED MEMORY DECLINE
Bibliographic record
Abstract
Abstract Background Age-related deterioration of cognitive function and memory capacity occur in both humans and rodents. For example, significant memory deficits have been reported in conventionally raised (SPF) old mice compared to conventionally raised young mice submitted to a spatial memory task (Prevot et al., 2019, Mol Neuropsychiatry 5, 84–97). Microbiota-to-brain signaling is now well established in mice and humans, but the extent to which it influences age-associated memory decline is unknown. Aims Our study examines whether the intestinal microbiota contributes to age-associated changes in brain function. We address the specific hypothesis that age-associated cognitive decline is attenuated in the absence of the intestinal microbiota. Methods We assessed anxiety-like and depressive-like behavior, locomotor activity and spatial memory performance in young germ-free (GF) mice (2–3 months of age, n=24) and senescent GF mice (13–27 months old, n=22) maintained in axenic conditions, and compared them to conventionally raised (SPF) mice of the same age. Anxiety-like behavior, locomotor activity and depressive-like behavior were measured using the light-dark preference, open-field, and tail suspension tests. We also used the Y-maze test based on a spontaneous alternation task to assess cognition, with the alternation rate as a proxy of spatial working memory. The age-associated inflammation was assessed with IL-6 cytokine plasma concentrations measured by ELISA. Results Anxiety-like behavior and depressive-like behavior did not change with the age regardless of the microbial status. However, old SPF mice traveled less distance (866.8 cm) than young SPF mice (1375 cm, p < 0.01) in the open-field. Similarly, old GF mice also traveled less distance (458.9 cm) than young GF mice (875.7 cm, p < 0.0001). In contrast to old SPF mice, old GF mice did not show memory impairment in the spatial memory task. Indeed, old SPF mice displayed lower alternation rate of 58.3%, compared to that found in young SPF mice (76.9%, p < 0.05) while both old and young GF mice had an identical alternation rate of 73.3% ( p > 0.05). In addition, IL-6 plasma levels revealed that old GF mice did not show signs of age-associated inflammation that was evident in old SPF mice (3.68 vs. 13.93 pg/ml, p < 0.05). Conclusions We conclude that the absence of age-related memory deficit in old germ-free mice is consistent with a role for the microbiota in age-related cognitive decline, likely mediated via the immune system, as suggested by the absence of age-associated inflammation in germ-free mice. We propose that novel microbiota-targeted therapeutic strategies may prevent or delay the cognitive decline of aging. Funding Agencies CIHRBalsam Family Foundation
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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 | 0.000 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".