Up‐regulation of `peripheral‐type' benzodiazepine receptors in the globus pallidus in manganese neurotoxicity
Bibliographic record
Abstract
Increasing evidence suggests that astrocytes play a major role in damage to the nervous system in manganese neurotoxicity (MN). Astrocytes accumulate manganese and sequester the metal in mitochondria where it inhibits oxidative phosphorylation. Chronic exposure to manganese leads to selective neuronal loss in basal ganglia structures such as the globus pallidus together with characteristic astrocytic changes known as Alzheimer type II astrocytosis. In previous reports we have demonstrated that treatment of these cells with manganese leads to increased binding site densities of the ‘peripheral‐type’ benzodiazepine receptor (PTBR) complex (Hazell et al. 1999; Neurosci. Lett. 271, 5–8), found predominantly in astrocytes and an important source of neurosteroid production. In the present study, we have examined the effects of manganese treatment in a subacute rat model of manganese neurotoxicity. Male Sprague–Dawley rats (200 g) were administered manganese (II) chloride (50 mg/kg, i.p. in 0.2 mL saline) daily for 1 and 4 days while control animals were injected with carrier only. Using neutron activation analysis, levels of manganese in the globus pallidus were found to be increased by 81% after 24 h of treatment but were elevated by 551% compared to controls after 4 days. Manganese treatment also led to a 110% increase in levels of the 18 kDa isoquinoline carboxamide‐binding protein, a major constituent of the PTBR, after 4 days but with no change in protein expression at 1 day by immunoblotting, consistent with the neutron activation findings. These results indicate that PTBRs and possibly neurosteroids are an early response to manganese exposure and may play a major role in the pathophysiology of MN.
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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) | 0.001 | 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".