Purinergic signalling is altered in the Fmr1-KO mouse hippocampus
Bibliographic record
Abstract
Fragile-X syndrome (FXS), the leading genetic cause of intellectual disability, occurs when the Fmr1 gene on the X-chromosome is silenced, reducing the levels of Fragile-X mental retardation protein (FMRP). This loss of FMRP hinders neurodevelopment and leads to several neurological pathologies, one of which is learning and memory deficits that are attributed to dysregulated hippocampal neurogenesis. The purinergic signalling pathway, where cells use ATP and its metabolites as signalling molecules, is essential for neurogenesis but has yet to be considered in the FXS hippocampus. However, our lab has discovered abnormal purinergic signalling in the FXS cortex, suggesting FMRP regulates this pathway. We hypothesize that purinergic signalling abnormalities exist in the FXS hippocampus and contribute to the dysregulation of neurogenesis. To begin our investigation, we used the Fmr1-KO mouse model to characterize the expression of purinergic receptors known to be involved in neurogenesis. After performing Western Blots on hippocampal tissue at postnatal day 1 (P1), P7, P14, and P21, we found that the P2X7 receptor was upregulated at P7. In mice, P7 is when hippocampal neurogenesis peaks; therefore, overexpression of P2X7 at this critical time point may have increased consequences for the adult mouse. Because P2X7 can play several roles in neurogenesis, it is unclear what those long-term consequences may be. Our next step is to determine which cells overexpress the P2X7 receptor to determine which aspect(s) of neurogenesis this P2X7 overexpression may impact.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".