Axonal degeneration induces distinct patterns of phosphatidylserine and phosphatidylethanolamine externalization
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Bibliographic record
Abstract
Abstract Axonal degeneration is a common feature of multiple neurodegenerative diseases, yet the mechanisms underlying its various manifestations are incompletely understood. We previously demonstrated that axonal degeneration is associated with externalization of phosphatidylserine (PS), which precedes morphological evidence of degeneration, is redox-sensitive, and is delayed in Wallerian degeneration slow (Wld S ) mutant animals. Phosphatidylethanolamine (PE) is the other major membrane phospholipid in the inner leaflet of the cell membrane, and given that PS signals apoptosis, phagocytosis, and degeneration, we hypothesized that PS and PE membrane dynamics play distinct roles in axonal degeneration. To test this hypothesis, axonal degeneration was induced with calcium ionophores in postnatal rat retinal ganglion cells, and PS- and PE-specific fluorescent probes used to measure their externalization over time. In untreated cells, cell-surface PS was prominent in the cell body alone. Elevation of intracellular calcium with calcium ionophores resulted in significantly increased levels of PS externalization in the cell body, axon, and axon growth cone. Unlike PS, cell-surface PE was diffusely distributed in untreated cells, with comparable levels across the soma, axons, and axon terminals. After exposure to calcium ionophores, PE externalization significantly increased in the cell body and axon. Elevated intracellular calcium also resulted in the formation of axonal blebs which exclusively contained externalized PS, but not PE. Together, these results indicated distinct patterns of externalized PS and PE in normal and degenerating neurons, suggesting a differential role for these phospholipids in transducing neuronal injury.
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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 | 0.000 | 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) | 0.000 | 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 it