B12 Treatment with arimoclomol does not lead to rescue of motor or striatal deficits in the YAC128 mouse model of Huntington's disease
Bibliographic record
Abstract
Background Huntington9s Disease (HD) is an inherited neurological disorder characterised by loss of motor coordination, cognitive dysfunction and psychiatric disturbances that remains without a cure. Arimoclomol, a compound reported to enhance cellular stress induced heat shock protein response, has been shown to be neuroprotective in a mouse model of amyotrophic lateral sclerosis (ALS). Aims To examine whether treatment with arimoclomol would (a) protect against quinolinic acid (QA) mediated excitotoxicity and (b) improve the phenotype of the YAC128 mouse model of HD. Methods 3 month old wild-type (WT) mice were pretreated with PBS or arimoclomol (40 mg/kg, intraperitoneally followed by an intrastriatal injection of QA (20 nmol) 30 min later). Striatal lesion volume in arimoclomol and PBS treated animals was assessed 7 days later. YAC128 and WT mice were treated with 80 mg/kg of arimoclomol administered in the drinking water for 10 months, starting at 2 months of age. YAC128 and WT animals receiving water only served as no treatment controls. Motor function was assessed using the accelerating and fixed speed rotarod tests at 2, 4, 6, 8, 10 and 12 months of age. Striatal pathology was assessed using unbiased stereology at 12 months of age. Results In animals that received intrastriatal injections of QA, there was no significant difference in lesion volume between those pretreated with arimoclomol compared with those treated with PBS only. In animals receiving arimoclomol chronically, there was no significant difference between arimoclomol treated and untreated WT animals in motor performance, as assessed by the accelerating and fixed speed rotarod tests. The motor performance of untreated YAC128 HD mice was significantly lower compared with that of untreated WT animals. Treatment with arimoclomol had no effect on motor performance of YAC128 HD animals compared with untreated YAC128 HD animals. Further, brain weight and striatal volume of untreated YAC128 HD animals was significantly lower compared with untreated WT animals. Treatment with arimoclomol had no effect on brain weight or striatal volume of YAC128 HD animals compared with untreated YAC128 HD mice. Conclusions Our findings demonstrate that treatment with arimoclomol does not lead to improvements in motor function or rescue of striatal pathology in YAC128 HD mice.
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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 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".