Abstract 1752 The Role of the Secreted Glycoprotein MFG-E8 in Astrocyte-Mediated Phagocytosis of Neurons
Bibliographic record
Abstract
Dysregulated synapse elimination is a hallmark of various central nervous system (CNS) diseases, including Alzheimer's disease (AD). Microglia, the resident professional phagocytes in the brain, have been the focus in the field of synapse elimination for upwards of a decade. However, astrocytes are also capable of phagocytosing synapses and participate actively in developmental synaptic pruning. Interestingly, astrocytes express an opsonin called milk fat globule epidermal growth factor-like factor 8 (MFG-E8), along with its receptor integrin αVβ5. MFG-E8 is known to mediate tissue reorganization, being a key player in mammary gland involution post-lactation. Additionally, integrin αVβ5 can crosstalk with the phagocytic receptor MERTK which has already been shown to initiate astrocytic phagocytosis of synapses. MFG-E8 has recently been shown to be overexpressed in AD, and to increase the engulfment of synaptic material by astrocytes and microglia. Yet, the mechanism through and conditions in which this occurs has not been fully elucidated. This work aims to further explore the function of MFG-E8 regarding astrocytic phagocytosis of synaptic material in particular, as astrocytes express MFG-E8 at higher levels than microglia and are very well placed for synaptic monitoring and pruning. To this end, an immunocytochemical assay was developed to measure phagocytosis of apoptotic neuronal model cells SH-SY5Y by the astrocyte model cell line U138-MG in the presence of recombinant MFG-E8. Using this method, the effects of MFG-E8 concentration, AD-like biochemical conditions, and phagocytic receptor blockers on the phagocytic capacity of U-138MG cells was measured, illuminating the role and result of the interactions between MFG-E8 and its receptor integrin αVβ5 in astrocyte-mediated phagocytosis of neurons. This research was funded in part by the National Science and Engineering Research Council of Canada (NSERC 2020-06103), the Lashley & Mary Haggman Memorial Research Award, and the University of British Columbia.
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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) | 0.004 | 0.002 |
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".