Impact of basic FGF expression in astrocytes on dopamine neuron synaptic function and development
Bibliographic record
Abstract
Behavioural sensitization to amphetamine (AMPH) requires action of the drug in the ventral midbrain where dopamine (DA) neurons are located. In vivo studies suggest that AMPH sensitization requires enhanced expression of basic fibroblast growth factor (bFGF) in the nucleus of midbrain astrocytes. One idea is that the AMPH-induced increase in bFGF expression in astrocytes leads to enhanced secretion of this peptide and to long-term plasticity in DA neurons. To study directly the effects of astrocytic expression of bFGF on DA neurons, we established a cell-culture model of mesencephalic astrocytes and DA neurons. Immunolabelling showed that even in the absence of a pharmacological stimulus, the majority of mesencephalic astrocytes in culture express bFGF at a nuclear level. Arguing against the idea that bFGF was secreted, bFGF was undetectable in the extracellular medium (below 10 pg/mL). However, supplementing culture medium with exogenous bFGF at standard concentrations (20 ng/mL) led to a dramatic change in the morphology of astrocytes, increased spontaneous DA release, and inhibited synapse formation by individual DA neurons. RNA interference (siRNA) against bFGF mRNA, caused a reduction in DA release but produced no change in synaptic development. Together these data demonstrate that under basal conditions (in the absence of a pharmacological stimulus such as amphetamine) bFGF is not secreted even though there is abundant nuclear expression in astrocytes. The effects of bFGF seen here on DA neurons are thus likely to be mediated through more indirect glial-neuronal interactions, leading to enhanced DA release without a necessary change in synapse number.
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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 | 0.001 |
| 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".