Chronic AMPK activation reduces synaptic plasticity markers in Neuronal SH‐SY5Y Cells
Bibliographic record
Abstract
Neuronal synapse function and growth rely on the abundance proteins at the synapse. This abundance is regulated by key metabolic markers: AMP‐Kinase (AMPK) and the Mechanistic Target of Rapamycin Complex 1 (mTORC1). AMPK is a serine/threonine kinase highly expressed in brain. When activated, AMPK stimulates catabolic processes, and inhibits anabolic processes through mTORC1 inhibition. Defects in AMPK signaling have been reported in peripheral metabolic disorders and the manipulation of AMPK activity has been an attractive therapeutic target for diseases in which altered energy metabolism contributes to etiology (Obesity type‐2‐diabetes). Recent evidence also suggests that impaired AMPK activity plays a role in Alzheimer's disease. However, there is ambiguity surrounding the role of AMPK activation in neuronal metabolic regulation and its affects on neuron growth and health. The objective of this study was to determine the direct effect of chronic AMPK modulation on markers related to synapse growth and function in a neuronal cell culture model. Retinoic acid differentiated (1g/mL) SH‐SY5Y Human Neuroblastoma cells were treated with: 1) Vehicle control; 2) A‐769662 (100uM; AMPK agonist); or 3) compound C (30uM; AMPK inhibitor). Cells were treated for 1, 3, and 5 days to examine chronic AMPK activation or inhibition. Cell lysates were collected for western blotting (WB) to examine AMPK activation (AMPK T172), a marker of mTORC1 formation and cellular proliferation (raptor), and markers of neurogenesis and pre/post‐synaptic proteins (synaptophysin, homer‐1, PSD‐95, synaptophysin, BDNF). PSD‐95, homer‐1, synaptophysin, and BDNF are significant markers in maintaining/developing proper synapse function and strength. AMPK T172 phosphorylation following treatment with A‐769662, was higher than control for all time points (24h, 3d, 5d) and resulted in higher raptor S792 phosphorylation compared to control, indicative of chronic mTORC1 inhibition. No changes in neuronal marker content was observed following 24h of AMPK activation. However, significant reductions were seen in PSD‐95, homer‐1, synaptophysin, and BDNF content following 3d and 5d of AMPK activation. Taken together, these findings indicate a role for AMPK activation in regulating key synaptic plasticity markers and highlights drawbacks in pursuing AMPK as a therapeutic target for metabolic diseases such as Alzheimer's disease.
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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) | 0.001 | 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) | 0.002 | 0.001 |
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".