Astrocyte-to-neuron H2O2 signalling supports long-term memory formation in Drosophila and is impaired in an Alzheimer’s disease model
Bibliographic record
Abstract
Abstract Astrocytes help protect neurons from potential damage caused by reactive oxygen species (ROS). While ROS can also exert beneficial effects, it remains unknown how neuronal ROS signalling is activated during memory formation, and whether astrocytes play a role in this process. Here we discover an astrocyte-to-neuron H 2 O 2 signalling cascade in Drosophila that is essential for long-term memory formation. Stimulation of astrocytes by acetylcholine induces an increase in intracellular calcium ions, which triggers the generation of extracellular superoxide (O 2 • – ) by astrocytic NADPH oxidase. Astrocyte-secreted superoxide dismutase 3 (Sod3) converts O 2 • – to hydrogen peroxide (H 2 O 2 ), which is imported into neurons of the olfactory memory centre, the mushroom body, as revealed by in vivo H 2 O 2 imaging. Notably, Sod3 activity requires copper ions, which are supplied by neuronal amyloid precursor protein. We also find that human amyloid-β peptide, implicated in Alzheimer’s disease, inhibits the nAChRα7 astrocytic cholinergic receptor and impairs memory formation by preventing H 2 O 2 synthesis. These findings may have important implications for understanding the aetiology of Alzheimer’s disease.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".