Chronic LiCl pretreatment suppresses thrombin‐stimulated intracellular calcium mobilization through<scp>TRPC</scp>3 in astroglioma cells
Bibliographic record
Abstract
Objectives Transient receptor potential canonical type 3 (TRPC3) channels are activated in B lymphoblast cell lines from patients with bipolar disorder (BD), and its expression is reduced by chronic lithium treatment, implicatingTRPC3 in the intracellular calcium (Ca2+) dyshomeostasis ofBD. Thrombin, via a protease‐activated receptor, moderates Ca2+signaling andTRPC3 in astrocytes, and also cell proliferation. We examined whether lithium pretreatment attenuates thrombin‐stimulatedTRPC3 expression and function in astrocytes, and levels of the calcium‐binding peptide, S100B, which is expressed mainly in these cells. Methods Human astroglioma, U‐87MG,cells were pretreated with 1 mmol L−1LiCl for 1 day (acute), 3 days (subacute), and 7 days (chronic). To examine the role ofTRPC3, genetically stable knockdownTRPC3 cells (TRPC3Lowcells) were constructed using U‐87MGcells. Thrombin (2.0 U/mL)‐stimulated Ca2+mobilization was measured by ratiometric fluorimetry. Changes inTRPC3 and S100B expression levels were determined by quantitative reverse transcription‐polymerase chain reaction and immunoblotting, respectively. Cell proliferation was also measured using theWST‐8 assay. Results In this cell model, thrombin‐stimulated Ca2+mobilization, and bothTRPC3 and S100B expression were suppressed by chronic LiCl pretreatment and the knockdown ofTRPC3. Additionally, cell proliferation was attenuated inTRPC3Lowcells, compared with the negative control vector‐transfected cell. Conclusions The reduced Ca2+mobilization and S100B expression levels following chronic LiCl pretreatment and inTRPC3Lowcells support the notion thatTRPC3 modulates S100B expression and is the target of the LiCl effect. Downregulation ofTRPC3 may be an important mechanism by which lithium ameliorates pathophysiological intracellular Ca2+disturbances as observed inBD, accounting, in part, for its mood‐stabilizing effects.
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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".