Role of Prefrontal Cortex Anti- and Pro-inflammatory Cytokines in the Development of Abnormal Behaviors Induced by Disconnection of the Ventral Hippocampus in Neonate Rats
Bibliographic record
Abstract
Neonatal disconnection of ventral hippocampus (VH) outputs in rats has been reported to lead to post-pubertal behavioral and synaptic changes of relevance to schizophrenia. Increased oxidative and inflammatory load in the prefrontal cortex (PFC) has been suggested to mediate some of the effects of neonatal VH lesion (NVHL). In this study, we hypothesized that developmental imbalance of anti- and pro-inflammatory factors within the PFC might affect synaptic development thus contributing to the adult NVHL-induced behavioral deficits. Ibotenic acid-induced excitotoxic NVHL was performed in postnatal day (PD) 7 male Sprague-Dawley rats and the mRNA levels of select pro- and anti-inflammatory cytokines were measured in the medial PFC (mPFC) at two developmental time points (PD15 and PD60). We observed a development-specific increase of pro-inflammatory cytokine, interleukin (IL)-1β mRNA at PD15, and an overall reduction in the expression and signaling of transforming growth factor beta 1 (TGF-β1), an anti-inflammatory cytokine, at both PD15 and PD60 in the NVHL animals. These cytokine changes were not seen in the somatosensory cortex (SSC) or tissue surrounding the lesion site. Daily administration of systemic recombinant TGF-β1 from PD7-14 prevented the appearance of hyperlocomotion, deficits in prepulse inhibition (PPI) of startle and social interaction (SI) in post-pubertal (PD60) NVHL rats. Neonatal supplementation of TGF-β1 was also able to attenuate dendritic spine loss in the layer 3 mPFC pyramidal neurons of NVHL animals. These results suggest that early damage of the VH has long-lasting inflammatory consequences in distant connected structures, and that TGF-β1 has potential to confer protection against the deleterious effects of developmental hippocampal damage.
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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 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".