Life-Course Contribution of Prenatal Stress in Regulating the Neural Modulation Network Underlying the Prepulse Inhibition of the Acoustic Startle Reflex in Male Alzheimer’s Disease Mice
Bibliographic record
Abstract
The prepulse inhibition (PPI) of the acoustic startle reflex (ASR), as an index of sensorimotor gating, is one of the most extensively used paradigms in the field of neuropsychiatric disorders. Few studies have examined how prenatal stress (PS) regulates the sensorimotor gating during the lifespan and how PS modifies the development of amyloid-beta (Aβ) pathology in brain areas underlying the PPI formation. We followed alternations in corticosterone levels, learning and memory, and the PPI of the ASR measures in APPNL-G-F/NL-G-F offspring of dams exposed to gestational noise stress. In-depth quantifications of the Aβ plaque accumulation were also performed at 6 months. The results indicated an age-dependent deterioration of sensorimotor gating, long-lasting PS-induced abnormalities in PPI magnitudes, as well as deficits in spatial memory. The PS also resulted in a higher Aβ aggregation predominantly in brain areas associated with the PPI modulation network. The findings suggest the contribution of a PS-induced hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in regulating the PPI modulation substrates leading to the abnormal development of the neural protection system in response to disruptive stimuli. The long-lasting HPA axis dysregulation appears to be the major underlying mechanism in precipitating the Aβ deposition, especially in brain areas contributed to the PPI modulation network.
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How this classification was reachedexpand
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".