Ketamine-induced neurotoxicity mediated through endoplasmic reticulum stress
Bibliographic record
Abstract
There is growing concern over the increased use of ketamine in recreational and therapeutic settings due to potential toxic effects. Recent studies have demonstrated that ketamine is cytotoxic in several cell lines, such as on nephrons, hepatocytes, and hippocampal cells. Ketamine has been shown to dysregulate the mitochondria and increase ROS production and DNA fragmentation leading to apoptosis. What remains unclear is the effects of ketamine on endoplasmic reticulum (ER) stress in striatal neurons. Perturbations to ER homeostasis, such as calcium dysregulation, can initiate ER-mediated cell death and is associated with neurodegeneration. Thus, we aimed to examine whether ketamine is neurotoxic through ER stress induction. Mouse striatal cells were treated with ketamine (10uM, 100uM, 1mM) for 12 to 72 hrs. Following treatment, intracellular Ca2+ was measured using fluorescence, and changes in ER genes were examined using RT-qPCR. After 24 hrs, 1mM ketamine was toxic to striatal cells, as demonstrated by a time-dependent decrease in cell viability compared to controls. Within 12 hrs, ketamine sustainably reduced intracellular Ca2+ levels and induced UPR activation that favoured pro-apoptotic signalling over cell survival. Upregulation of GRP78, the master regulator of ER stress, was observed up to 24 hrs, while prolonged exposure decreased expression. Further, upregulation of pro-apoptotic UPR protein CHOP was shown throughout the experiment. Together, these findings demonstrate that ketamine-induced neurotoxicity is partially mediated through ER stress-induced apoptosis.
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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) | 0.002 | 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".