Low and High Molecular Weight FGF-2 Have Differential Effects on Astrocyte Proliferation, but Are Both Protective Against Aβ-Induced Cytotoxicity
Bibliographic record
Abstract
Astrocytes are the most abundant type of glial cells in the brain, and they play a key role in Alzheimer’s disease (AD). Fibroblast Growth Factor-2 (FGF-2) has been implicated as a potential therapeutic agent for treating AD. In the present study, we investigated the protective effects of low molecular weight (17KDa) and high molecular weight (23KDa) forms of FGF-2 on Aβ1-42-induced toxicity, and proliferation in astrocytes. We show that both isoforms of FGF-2 have similar protective effects against Aβ1-42-induced cytotoxicity in primary cultured cortical astrocytes as measured by LDH release assay. Additionally, 17KDa FGF-2 significantly promoted astrocyte proliferation as measured by Trypan Blue, DRAQ5 staining, ki67 and Edu immunocytochemistry, but not 23kDa FGF-2. Furthermore, our results demonstrated that AKT signaling pathway was required for the protective and proliferative effects of FGF-2. Downstream effector studies indicated that 17kDa FGF-2 promoted astrocyte proliferation by hyper-phosphorylation of AKT at Thr308 residue and enhanced expression of c-Myc, Cyclin D1, Cyclin E. Furthermore, our data suggest that Cyclin D1 is required for the proliferative effect of LMW FGF2 in astrocytes. Taken together, our findings showing differential effects of 23kDa and17kDa isoforms of FGF-2 on astrocyte protection and promotion of proliferation, provide important information for determining the form of FGF-2 that will be most appropriate for potential treatment 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 | 0.000 | 0.001 |
| 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 | 0.001 | 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".