Subthalamic nucleus deep brain stimulation is neuroprotective in the A53T α‐synuclein Parkinson's disease rat model
Bibliographic record
Abstract
Objective Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a highly effective symptomatic therapy for motor deficits in Parkinson's disease (PD). An additional, disease‐modifying effect has been suspected from studies in toxin‐based PD animal models, but these models do not reflect the molecular pathology and progressive nature of PD that would be required to evaluate a disease‐modifying action. Defining a disease‐modifying effect could radically change the way in which DBS is used in PD. Methods We applied STN‐DBS in an adeno‐associated virus (AAV) 1/2‐driven human mutated A53T α‐synuclein (aSyn)‐overexpressing PD rat model (AAV1/2‐A53T‐aSyn). Rats were injected unilaterally, in the substantia nigra (SN), with AAV1/2‐A53T‐aSyn or control vector. Three weeks later, after behavioral and nigrostriatal dopaminergic deficits had developed, rats underwent STN‐DBS electrode implantation ipsilateral to the vector‐injected SN. Stimulation lasted for 3 weeks. Control groups remained OFF stimulation. Animals were sacrificed at 6 weeks. Results Motor performance in the single pellet reaching task was impaired in the AAV1/2‐A53T‐aSyn–injected stim‐OFF group, 6 weeks after AAV1/2‐A53T‐aSyn injection, compared to preoperative levels (–82%; p < 0.01). Deficits were reversed in AAV1/2‐A53T‐aSyn, stim‐ON rats after 3 weeks of active stimulation, compared to the AAV1/2‐A53T‐aSyn stim‐OFF rats (an increase of ∼400%; p < 0.05), demonstrating a beneficial effect of DBS. This motor improvement was maintained when the stimulation was turned off and was accompanied by a higher number of tyrosine hydroxylase + SN neurons (increase of ∼29%), compared to AAV1/2‐A53T‐aSyn stim‐OFF rats ( p < 0.05). Interpretation Our data support the putative neuroprotective and disease‐modifying effect of STN‐DBS in a mechanistically relevant model of PD. Ann Neurol 2017;81:825–836
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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 | 0.000 |
| 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".