Transforming growth factor β1 differently modulates wild‐type and TgF344‐AD astrocyte cultures' function
Bibliographic record
Abstract
Abstract Background Astrocytes are key players involved in several functional aspects of the brain. They manage extracellular neurotransmitters and ions, regulate blood flow and energy substrates. Additionally, they produce and release growth factors, with autocrine and paracrine reach. Recently, the beneficial effects of Transforming Growth Factor β1 (TGF‐β1) have been shown in some experimental models of neurodegenerative diseases. However, the effects of TGF‐β1 in experimental models of Alzheimer’s Disease (AD) are still a matter of debate and further mechanistic investigation is needed. Here, we used adult astrocyte cultures prepared for the first time from Fischer TgF344‐AD (TG) rats to verify whether exogenous TGF‐β1 would affect astrocyte function. Method Cortices of adult (4‐month‐old) Fischer wild‐type (WT) and TG rats were aseptically dissected and digested with trypsin and papain. Cells suspensions were plated in 24‐well plates and cultivated for 3 weeks in DMEM/F12 supplemented with 10‐20% fetal bovine serum (FBS). At confluence, cells were treated with TGF‐β1 10 ng/mL for 1, 4 or 24h in DMEM/F12 1% FBS. Glutamate uptake was measured by radioactive assay and cellular morphology was evaluated with glial fibrillary acidic protein (GFAP) antibody and with rhodamine‐phalloidin for actin staining. Result Astrocytes from WT and TG rats take up the same amount of glutamate in basal conditions. WT astrocytes, however, respond to TGF‐β1 treatment increasing the levels of glutamate uptake nearly two‐fold after been treated for 4 or 24h (p<0.05), while TG astrocytes are not affected. GFAP and actin staining of the astrocytes shows extensive expression of the glial marker in the cytoskeleton and typical morphology (Figure 1 ‐ representative of TG astrocytes). Conclusion TGF‐β1 enhanced glutamate uptake in WT but not in TG astrocytes. This may be related to an intrinsic lesser ability to fulfill neuroprotective roles and decreased plasticity presented by TG astrocytes. Impaired astrocyte function is thought to be a decisive component of AD and here we show preliminary data that suggests decreased capacity of TG astrocytes to respond to neuroprotective compounds such as TGF‐β1. Whether the decreased response to TGF‐β1 is contributing to neurodegeneration or it is a consequence of neurotoxic stimulus in TG cells remains to be determined.
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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) | 0.001 | 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 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".