Neurobiological effects of sphingosine 1‐phosphate receptor modulation in the cuprizone model
Why this work is in the frame
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Bibliographic record
Abstract
Fingolimod (FTY720) is a sphingosine 1-phosphate (S1P) receptor modulator that regulates lymphocyte trafficking and exerts pleiotropic actions on oligodendrocytes (OLGs) and other neural cells. The purpose of this study was to investigate the role of S1P receptors in a non-T-cell model of demyelination, the cuprizone (cupr) model in C57BL/6 mice. Treatment with FTY720 (1 mg/kg) led to attenuated injury to OLGs, myelin, and axons in the corpus callosum (percentage of myelinated fibers was 44.7% in cupr-water and 63% in cupr-FTY720). Reactive astrogliosis and microgliosis were ameliorated when FTY720 was given from d 1, but astrogliosis was augmented when FTY720 was given from wk 4-9. FTY720 did not promote remyelination in this model. The protective effect of FTY720 was associated with decreased interleukin-1β and CCL2 transcripts in the corpus callosum, as well as altered S1P1 expression. Targeted deletion of S1P1 in OLG lineage cells did not lead to obvious clinical phenotype, but resulted in subtle abnormalities in myelin and an increased susceptibility to cupr-induced demyelination. We conclude that S1P receptors expressed by neuroglia are involved in regulating the response to injury, and CNS effects of FTY720 could contribute to its favorable therapeutic response in multiple sclerosis.
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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 | 0.001 | 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