Glyphosate‐based herbicide alters brain amino acid metabolism without affecting blood‐brain barrier integrity
Bibliographic record
Abstract
Abstract Background Glyphosate‐based herbicides (GBH) are the most widely used pesticides, mainly due to their use in genetically modified crops. Lately, GBH induced‐neurotoxic effects are gaining attention since they are potential risk factors for developing neurodegenerative diseases, including Alzheimer’s disease (AD). It has been shown that GBH exposure is associated to brain glutamatergic excitotoxicity ‐ a key pathological feature in AD, which may cause blood‐brain barrier (BBB) breakdown. In addition, the activity of some urea cycle enzymes and arginine downstream metabolites seem to be altered in AD patient brains. Based on that, we aimed at evaluating central and peripheral effects of GBH acute exposure. Method GBH was administered into adult male Wistar rats (90 day‐old, n = 14) in a single oral dose (400 mg/kg). The AA and albumin levels in CSF were assessed by High‐Performance Liquid Chromatography in control conditions and 3, 24 and 48 h after administration. Serum urea content was measured by colorimetric assay. L‐[ 3 H]glutamate uptake and AA release were measured in tissue slices of parietal cortex, hippocampus and striatum to better understand alterations in 3 h (n = 8). Result CSF levels of excitatory AA aspartate and glutamate, as well as ornithine ‐ a downstream arginine metabolite ‐ were elevated 3 h after GBH exposure (Figures 1A, 1D). Accordingly, high levels of ornithine were released from slices of all brain regions in the same time point (Figure 1B). We did not observe changes in serum urea, CSF albumin levels (Figure 1C) and L‐[ 3 H]glutamate uptake. Conclusion We hypothesize that GBH directly affects brain AA metabolism regardless of its effects in the periphery, since we observed changes in CSF AA levels independently of BBB breakdown. Additionally, no changes in serum urea were observed, which points to a normal function of the urea cycle and a higher production/release of ornithine from brain cells. This suggests a potential unbalance in excitatory amino acids and arginine downstream metabolism as an effect of GBH exposure, which could contribute to GBH‐induced neurotoxicity. This work is in progress and we intend to characterize GBH long‐term exposure effects and its possible contribution to the pathogenesis and/or progression of AD.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| 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 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".