Induction of proinflammatory molecules in mice with amyotrophic lateral sclerosis: No requirement for proapoptotic interleukin‐1β in neurodegeneration
Bibliographic record
Abstract
Recent studies have demonstrated the activation of caspase-1 and caspase-3 in mice expressing mutant superoxide dismutase 1 (SOD1), models of amyotrophic lateral sclerosis. Caspase-1 converts the prointerleukin-1beta into a potent proinflammatory molecule involved in the innate immune response and in neurodegenerative diseases. We report on the chronic expression of interleukin-1beta mRNA in the spinal cord of SOD1G37R mice, together with robust mRNA expression for the nuclear factor-kappaB (NF-kappaB) inhibitor IkappaBalpha, for other proinflammatory cytokines and chemokines (interleukin-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1) and for the toll-like receptor TLR2 involved in innate immunity. To further assess the interleukin-1beta contribution to neurodegeneration, we generated mice expressing SOD1G37R in a context of interleukin-1beta gene knockout. Surprisingly, the absence of interleukin-1beta had no effect on the life span of SOD1G37R mice, nor on the extent of motor axon degeneration at age 7 and 10 months. Whereas neither compensatory induction of the interleukin-1alpha mRNA nor increases in mRNA levels for IkappaBalpha, tumor necrosis factor-alpha and macrophage chemoattractant protein-1 occurred as a result of interleukin-1beta gene disruption, enhanced levels of TLR2 mRNA were detected in SOD1G37R mice lacking interleukin-1beta. We conclude that interleukin-1beta does not directly contribute to motor neuron degeneration in SOD1G37R mice, but it may act as a modulator of the innate immune response.
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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 | 0.000 |
| 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 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".