Adenosine produced by neurons is metabolized to hypoxanthine by astrocytes
Bibliographic record
Abstract
Adenosine (ADO) is an important neuromodulator in brain. During pathophysiological events such as stroke or brain trauma, ADO levels can increase up to 100-fold. We tested the hypothesis that astrocytes are important for the removal of ADO produced by neurons and for the metabolism of ADO to inosine (INO) and hypoxanthine (HX). We used four different cell culture preparations: cortical neurons, cortical astrocytes, cocultures of neurons and astrocytes, and neurons transiently cocultured with astrocytes on transwell filters. These cultures were treated with N-methyl-D-aspartate (NMDA), because NMDA receptor activation is a common factor among many causes of neurotoxicity. NMDA significantly increased extracellular ADO, INO, and HX levels from cultured cortical neurons by 3-, 3.5-, and 2-fold, respectively. In cocultures, NMDA significantly increased INO, by 4.5-fold, and HX, by 3-fold, but did not increase ADO levels. There was no NMDA-evoked purine production from astrocytes. Inhibition of purine nucleoside phosphorylase (PNP) significantly decreased HX production from both neurons and cocultures to less than 30% of control levels. The transient addition of astrocytes to neurons during NMDA treatment significantly increased HX and decreased ADO levels compared with neurons alone. In addition, increasing the number of astrocytes was directly correlated with an increased capacity of ADO metabolism to INO and HX. In conclusion, NMDA evoked the production of ADO, INO, and HX from neurons. In the presence of astrocytes, there was significantly less ADO and more HX produced. Thus, ADO produced by neurons is subject to metabolism by astrocytes, a process that may limit its neuromodulatory actions.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".