IC‐P‐001: Early treatment with pioglitazone in APP transgenic mice shows focal hippocampal volume increase related to improved cognitive performance
Bibliographic record
Abstract
Short-term pioglitazone treatment normalized cerebrovascular function in old APP mice (line J20), but not cognitive performance, presumably due to irreversible damage (Nicolakakis et al, 2008). Hence, a more favorable response might be elicited by earlier and longer treatment. At 3-months of age, APP mice display cerebrovascular deficits and marginal memory impairments, whereas robust memory deficits are seen at 6-months (DeIpolyi et al., 2008). We confirmed the rescue of activity-induced functional hyperemia by pioglitazone in young APP mice, and are now evaluating pioglitazone effects on cognitive performance and brain structure. Three-month-old APP and wildtype (WT) mice were treated with either pioglitazone or control diet (12 weeks, 20 mg/kg/day). Thereafter, mice were trained on one of two versions of the Morris Water Maze (MWM): (1) striatum-based non-spatial MWM with visible platform and no distal cues, or (2) hippocampal-based spatial MWM with hidden platform and distal visual cues. Performance was assessed using escape latencies and probe trial parameters. Ten days post-training, mice were transcardially perfused. Brains within intact skulls were post-fixed and imaged using high-resolution (32 micron isotropic) T2-weighted MRI at 7T. Deformation-based morphometry (DBM) was used to identify focal volume changes correlated with cognitive task performance using a general linear model (Lerch et al, 2008). All mice undergoing the non-spatial MWM performed equally well. Focal volume increase associated with non-spatial MWM was observed in the striatum. On spatial MWM, APP mice displayed significantly prolonged escape latencies to reach the hidden platform compared to WT. Pioglitazone-treated APP mice exhibited a trend for reduced latencies during training, and a slightly higher number of platform-crossings than untreated APP mice during probe trial. Focal volume increase associated with spatial MWM performance was observed in the hippocampus in WT mice and treated APP mice, but not in untreated APP mice. We have demonstrated using high resolution MRI and DBM that spatial learning-induced hippocampal brain plasticity is absent in young APP mice. Pioglitazone-treatment in young APP mice had beneficial effects on focal hippocampal volume growth associated with spatial MWM performance, and completely rescued cerebrovascular function, suggesting that early and continued pioglitazone treatment may slow AD progression.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".