Containment of neuroimmune challenge by diosgenin confers amelioration of neurochemical and neurotrophic dysfunctions in ketamine-induced schizophrenia in mice
Bibliographic record
Abstract
Inhibition of neuroinflammation through N-methyl-D-aspartate receptor (NMDAR) regulation can provide normalization of neurochemical homeostasis and neurotrophic support in the pathogenesis of psychiatric disorders with complex symptoms such as schizophrenia. Accordingly, the preventive and reversal effects and potential mechanisms of diosgenin, a phyto-steroidal sapogenin with anti-inflammatory functions, was evaluated in ketamine (an NMDAR antagonist) model of schizophrenia in mice. Adult male mice were allotted into 5 groups. In the preventive protocol, mice received saline (10 mL/kg), diosgenin (25 and 50 mg/kg) and risperidone (0.5 mg/kg) orally for 14 days, with additional injection of ketamine (20 mg/kg/day/i.p.) from days 8-14. In the reversal protocol, mice took ketamine injection consecutively for 14 days prior to diosgenin and risperidone treatments from days 8-14. Thereafter, schizophrenia-like behavior, therapeutic extrapyramidal adverse effect, neuroimmune, neurochemical and neurotrophic consequences in important brain areas affected in the disorder were assayed. Diosgenin prevents and reverses stereotypy behavior, cognitive impairment, and psychotic-depression relative to ketamine groups. Complementarily, diosgenin prevents and reverses ketamine-induced dopamine and serotonin alterations in the striatum, prefrontal-cortex, and hippocampus. Except for the cortical regions, diosgenin prevented and reversed depletions of glutamic acid decarboxylase in these brain regions by ketamine, suggesting improved GABAergic system. Additionally, ketamine-induced elevation of neuroinflammatory markers: myeloperoxidase, tumor necrosis factor-alpha and interleukin-6, were inhibited in the striatum, prefrontal-cortex, and hippocampus. Also, diosgenin improved the levels of neurotrophic factor in the three brain regions in both protocols respectively. Among other mechanisms, the antipsychotic effect of diosgenin might be associated with attenuation of neurochemical and neuroimmune alterations.
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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 | 0.001 |
| 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".