Neonatal maternal separation causes depressive-like behavior and potentiates memory impairment induced by amyloid-β oligomers in adult mice
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Bibliographic record
Abstract
BACKGROUND: Alzheimer's disease (AD) is characterized by memory decline and mood alterations. A growing body of evidence implicates stress and other social determinants of health as potential contributors to the progressive cerebral alterations that culminate in AD. In the current study, we investigated the impact of neonatal maternal separation (MS) on the susceptibility of male and female mice to AD-associated memory impairments and depressive-like behavior in adulthood, and on brain levels of pro-inflammatory cytokines and neurotransmitters. METHODOLOGY: Male and female Swiss mice were exposed to MS for 180 min daily from post-natal day 1 to 10. Seventy days post-MS, mice received an intracerebroventricular infusion of amyloid-β oligomers (AβOs), and memory and mood were evaluated. Levels of TNF-α, IL-1β, serotonin, dopamine, and related metabolites were determined in the cortex and hippocampus. RESULTS: Previous exposure to MS alone did not cause memory impairments in adult mice. Interestingly, however, MS increased the susceptibility of adult male mice to memory impairment and depressive-like behavior induced by AβOs, and potentiated the inhibitory impact of AβOs on memory in adult females. Females were more susceptible to depressive-like behavior caused by a low dose of AβOs, regardless of MS. No changes in IL-1β were found. A decrease in TNF-α was selectively found in females exposed to MS that received an infusion of 1 pmol AβOs. MS led to an increase in serotonin (5-HT) in the hippocampus of male mice, without influencing the levels of the serotonin metabolite, 5-HIAA. Changes in serotonin turnover were predominantly observed in the cortex of female mice. No changes in dopamine or its metabolites were induced by MS or AβOs in male or female mice. CONCLUSIONS: Neonatal MS enhances the susceptibility of adult mice to AD-associated cognitive deficits and depressive-like behavior in a sex-specific manner. This suggests that early life stress may play a role in the development of AD.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it