Large-scale effects of prenatal inflammation and early life circadian disruption in mice: Implications for neurodevelopmental disorders
Bibliographic record
Abstract
• Sex-specific effects of maternal immune activation (MIA) and circadian disruption. • Abnormal light exposure (LL) during adolescence modulates behavioral impact of MIA. • MIA/LL affect microglia morphology and associate with microglia gene signatures. • MIA increases differentially expressed hippocampal genes, which is attenuated by LL. • MIA/LL-affected genes overlap with neurodevelopmental disorder-related genes in GWAS. Around 80 % of individuals with neurodevelopmental disorders such as schizophrenia and autism spectrum disorders experience disruptions in sleep/circadian rhythms. We explored whether environmental circadian disruption interacts with prenatal infection, a risk factor for neurodevelopmental disorders, to induce sex-specific deficits in mice. A maternal immune activation (MIA) protocol was used by injecting pregnant mice with viral mimic poly IC or saline at E9.5. Juvenile/adolescent male and female offspring (3–7 weeks old) were then subjected to a standard light:dark cycle (12:12LD) or to constant light (LL). Significant interactions between treatment (MIA, control) and lighting (12:12LD, LL) were evident in behaviors related to cognition, anxiety, and sociability. This pattern persisted in our RNA sequencing analysis of the dorsal hippocampus, where poly IC exposure resulted in numerous differentially expressed genes (DEGs) in males, while exposure to both poly IC and LL led to a marked reduction in DEGs. Through WGCNA analysis, many significant gene modules were found to be positively associated with poly IC (vs. saline) and LL (vs. LD) in males (fewer in females). Many of the identified hub-bottleneck genes were homologous to human genes associated with sleep/circadian rhythms and neurodevelopmental disorders as revealed by GWA studies. The MIA- and LL-associated modules were enriched in microglia gene signatures, which was paralleled by trends of effects of each of the factors on microglia morphology. In conclusion, in a mouse model of prenatal infection, circadian disruption induced by LL during adolescence acts as a modulator of the effects of MIA at behavioral, cellular, and molecular levels.
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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) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".