Loss of brain insulin production impairs learning and memory in female mice
Bibliographic record
Abstract
Abstract Aims/hypothesis Diabetes is characterised by dysfunctional insulin release and action, and it is a risk factor for Alzheimer’s disease, the most common form of dementia. Alterations in brain insulin signalling and metabolism have been linked with Alzheimer’s disease. We hypothesised that loss of brain insulin might alter learning and memory performance. Methods We used qPCR, immunofluorescence and western blot analysis to confirm that the ancestral insulin gene, Ins2 , is transcribed within the brain, including in the hippocampus. To determine how locally produced insulin influences hippocampal function, we used mice with germline Ins2 knockout ( Ins2 −/− ) and the normal complement of wild-type Ins1 alleles. Compensation from the Ins1 gene ensured normal glucose tolerance, normal insulin sensitivity, normal fasting insulin and normal body weight under these diet and housing conditions. We analysed visuo-spatial learning and memory performance using the Morris water maze. We used RNA sequencing to provide unbiased analysis of gene expression in isolated hippocampi. Results Hippocampal Ins2 mRNA was higher in female mice than in males, and was modulated by diet. Learning and memory were significantly impaired in female Ins2 −/− mice relative to wild-type mice, while the performance of male Ins2 −/− and wild-type mice did not differ. RNA sequencing showed that cyclin D1 ( Ccnd1 ) was significantly reduced in Ins2 −/− mice. Conclusions/interpretation Our data point to female-specific roles for brain-derived Ins2 in learning and memory function in mice. Graphical Abstract
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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) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".