The role of thioredoxin-interacting protein in corticosterone-impaired neurite outgrowth
Bibliographic record
Abstract
Background: Glucocorticoid is produced in response to stress. Chronic stress is a high risk factor for developing psychiatric disorders. Many studies have shown that chronic stress and chronic treatment with stress hormone corticosterone cause oxidative damage in the brain. Thioredoxin is an oxidoreductase that reduces protein cysteine oxidation. Thioredoxin also facilitates peroxiredoxin-induced scavenging of H2O2, preventing protein cysteine oxidation and carbonylation. Trx can also bind to apoptosis signal-regulating kinase 1 (ASK1) and inhibit apoptosis. Thioredoxin-interacting protein (Txnip) is an endogenous thioredoxin inhibitor, promoting protein cysteine oxidation and carbonylation, and activating ASK1 apoptotic signaling. Previously, our laboratory found that chronic corticosterone treatment had no effect on thioredoxin levels, but increased Txnip levels in cultured mouse neurons, indicating that corticosterone may upregulate Txnip and cause oxidative damage to neurons. Objective: Establishing if chronic corticosterone treatment increases Txnip, causing oxidative protein damage and impairing neurite outgrowth. Methods and Results: Using immunoblotting analysis we found that although chronic treatment with corticosterone for 5 days had no effect on Trx, this treatment dose-dependently increased Txnip levels in primary cultured mouse cerebrocortical neurons. Using dimedone conjugation, biotin hydrazide conjugation and biotin-switch methods respectively, we also found that chronic corticosterone treatment increased protein cysteine sulfenylation and protein carbonylation, but had no effect on protein cysteine nitrosylation. We also found that chronic corticosterone had no effects on ASK phosphorylation, cell viability. Cultured neurons were stained by microtubule-associated protein 2 antibody using immunocytochemistry to analyze neurite outgrowth. We found that chronic corticosterone treatment reduced length and number of neurite branches. To determine the role of Txnip in corticosterone-induced neurite damage, Txnip genes were knocked down by CRISPR/Cas9/Txnip sgRNA technique. We found that knocking down Txnip prevented corticosterone-reduced length and number of neurite branches. Conclusion: Our findings suggest that chronic corticosterone treatment upregulates Txnip, promoting protein oxidative damage and impairing neurite outgrowth; and also suggest that Txnip may be a potential target for the treatment of psychiatric disorders.
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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) | 0.000 | 0.001 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".