Effects of fumarates on inflammatory human astrocyte responses and oligodendrocyte differentiation
Bibliographic record
Abstract
Abstract Objective Dimethyl fumarate ( DMF ) is a fumaric acid ester approved for the treatment of relapsing‐remitting multiple sclerosis ( RRMS ). In both the brain and periphery, DMF and its metabolite monomethyl fumarate ( MMF ) exert anti‐inflammatory and antioxidant effects. Our aim was to compare the effects of DMF and MMF on inflammatory and antioxidant pathways within astrocytes, a critical supporting glial cell in the central nervous system ( CNS ). Direct effects of fumarates on neural progenitor cell ( NPC ) differentiation toward the oligodendrocyte lineage were also assessed. Methods Primary astrocyte cultures were derived from both murine and human brains. Following pretreatment with MMF , DMF , or vehicle, astrocytes were stimulated with IL ‐1 β for 24 h; gene and micro RNA expression were measured by qPCR . Cytokine production and reactive oxygen species ( ROS ) generation were also measured. NPC s were differentiated into the oligodendrocyte lineage in the presence of fumarates and immunostained using early oligodendrocyte markers. Results In both murine and human astrocytes, DMF , but not MMF , significantly reduced secretion of IL ‐6, CXCL 10, and CCL 2; neither fumarate promoted a robust increase in antioxidant gene expression, although both MMF and DMF prevented intracellular ROS production. Pretreatment with fumarates reduced micro RNA s ‐146a and ‐155 upon stimulation. In NPC cultures, DMF increased the number of O4 + and NG 2 + cells. Interpretation These results suggest that DMF , and to a lesser extent MMF , mediates the anti‐inflammatory effects within astrocytes. This is supported by recent observations that in the inflamed CNS , DMF may be the active compound mediating the anti‐inflammatory effects independent from altered antioxidant gene expression.
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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 | 0.001 |
| 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 | 0.001 |
| 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".