Abnormalities in BDNF/TrkB/PI3K signaling pathways in autism (728.3)
Bibliographic record
Abstract
Cortical connectivity and spine abnormalities may account for clinical features of autism. BDNF, a key spine regulator, exhibits altered isoform balance in autism. Here, we investigated whether BDNF receptors and their signaling pathways are disrupted in post‐mortem fusiform gyrus from subjects with autism compared to controls and in the valproic acid (VPA)‐induced rat model of autism. Protein levels were examined by Western blot in 11 autism vs 13 control subjects and in lateral temporal neocortices of VPA rats vs controls. Reduced TrkB, PI3K, Akt, mTOR, phospho‐mTOR, p70S6K, eIF4B and PSD‐95 and a trend towards increased truncated TrkB and p75 NTR , but no changes in 4E‐BP1 or eIF4E, were found in autism subjects versus controls. Similar deficits were observed in VPA rats, although total and phospho‐4E‐BP1 were decreased in these rats. These findings suggest imbalances in BDNF/TrkB/PI3K and proBDNF/p75 NTR signaling in autism which could lead to spine defects. Reduced Akt‐mTOR protein and signaling, suggesting spine protein synthesis deficits, were observed in both autism and VPA rats, despite minor differences in down‐regulated signaling cascades. The resulting spine defects might lead to loss of excitatory synapses/decreased PSD‐95 in autism. Reduced excitatory synapses might perturb cortical circuitry, contributing to autism’s cognitive and behavioral deficits.
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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 | 0.001 | 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 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".