Assessment of motor neuron pathology and potential compensatory mechanisms in phenotypically normal mice with reduced Survival Motor Neuron levels.
Bibliographic record
Abstract
Spinal muscular atrophy (SMA) is a destructive pediatric neuromuscular disorder caused by low survival motor neuron (Smn) protein levels due to mutations and deletions within the survival motor neuron 1 (SMN1) gene. Motor neurons are the main pathological targets, and along with neuromuscular junctions (NMJs), they play an early significant role in the pathogenesis of SMA. Previous studies demonstrate that a pathological reduction in Smn levels can lead to significant remodeling defects in both the outgrowth of axonal sprouts and in the nerve-directed clustering of AChRs in mouse models. However, whether this pathological reduction in Smn leads to ubclinical features has not been investigated. Here, we have employed the Smn2B/2B and Smn+/- mouse models to study whether similar SMA pathology is present sub-clinically, and if so whether there is any compensation present. We show a decrease in the motor neuron number in the mouse models, no change in myelin thickness and modest NMJ pathology in both mouse models. Additionally, compensation through the expansion of the motor unit size is suggested.L’amyotrophie spinale (AMS) est un trouble neuromusculaire pédiatrique destructif causé par le niveau bas de protéine du neurone de moteur de survie (NMS) en raison des mutations et des effacements dans le neurone de moteur de survie 1 gène (NMS1). Des neurones du moteur sont les cibles pathologiques principales, et ce, avec des jonctions neuromusculaires (JNMs), ils jouent, en avance, un rôle significatif dans la pathogénie de AMS. Des études précédentes démontrent qu’une réduction pathologique de niveaux de NMS peut mener aux défauts importants de réorganisation tant dans l’excroissance axonale que dans l’agrégation du récepteur de l’acétylcholine (AChR) sous la terminaison nerveuse dans des modèles de souris. Cependant, si cette reduction pathologique de NMS mène aux caractéristiques infracliniques n’a pas été à l’étude. Ici, nous avons employé le NMS2B/2B et NMS +/- des modèles de souris afin de déterminer si une pathologie semblable à l’AMS est présente infracliniquement, ainsi s’il y a présence de quelconque compensation. Nous montrons une diminution dans le nombre des neurones du moteur dans les modèles de souris, aucun changement de l’épaisseur du myelin et une pathologie modeste de JNM dans les deux modèles de souris. De plus, une compensation par l’expansion de la taille d’unité du moteur est suggérée.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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".