Disruption of BDNF-TrkB signaling in spinocerebellar ataxia type 6
Bibliographic record
Abstract
Spinocerebellar ataxia type 6 (SCA6) is a rare disease that currently has no cure.It is caused by a CAG expansion mutation in the CACNA1A gene that encodes a subunit of the P/Q voltage-gated calcium channel, as well as the transcription factor α1ACT.SCA6 primarily affects the cerebellum, a region of the brain that is implicated in motor coordination and other behaviours.SCA6 patients present with cerebellar atrophy and have difficulties with motor coordination.These alterations are also present in mouse models of SCA6, including the SCA6 84Q/84Q mouse model which displays motor coordination deficits and cerebellar Purkinje cell firing abnormalities at 7 months of age, as well as later cerebellar degeneration.I used the SCA6 84Q/84Q mouse model to characterize molecular changes that occur in the SCA6 cerebellum, in order to identify therapeutic targets.I found that the levels of the signaling protein brain-derived neurotrophic factor (BDNF) and its receptor Tropomyosin receptor kinase B (TrkB) were reduced in the SCA6 cerebellum.I was able to restore BDNF-TrkB signaling with two methods, both of which rescued behavioural and Purkinje cell firing deficits in SCA6 84Q/84Q mice.First I tested a program of voluntary exercise on running wheels that was able to increase BDNF levels in the cerebellum of the SCA6 84Q/84Q mice.This intervention rescued motor coordination and Purkinje cell firing deficits when the treatment was started before motor deficits became pronounced.However, as the disease progressed, the
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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) | 0.000 | 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) | 0.004 | 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".