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 ( TRPC 3) channels are activated in B lymphoblast cell lines from patients with bipolar disorder ( BD ), and its expression is reduced by chronic lithium treatment, implicating TRPC 3 in the intracellular calcium (Ca 2+ ) dyshomeostasis of BD . Thrombin, via a protease‐activated receptor, moderates Ca 2+ signaling and TRPC 3 in astrocytes, and also cell proliferation. We examined whether lithium pretreatment attenuates thrombin‐stimulated TRPC 3 expression and function in astrocytes, and levels of the calcium‐binding peptide, S100B, which is expressed mainly in these cells. Methods Human astroglioma, U‐87 MG, cells were pretreated with 1 mmol L −1 LiCl for 1 day (acute), 3 days (subacute), and 7 days (chronic). To examine the role of TRPC 3, genetically stable knockdown TRPC 3 cells ( TRPC 3 Low cells) were constructed using U‐87 MG cells. Thrombin (2.0 U/mL)‐stimulated Ca 2+ mobilization was measured by ratiometric fluorimetry. Changes in TRPC 3 and S100B expression levels were determined by quantitative reverse transcription‐polymerase chain reaction and immunoblotting, respectively. Cell proliferation was also measured using the WST ‐8 assay. Results In this cell model, thrombin‐stimulated Ca 2+ mobilization, and both TRPC 3 and S100B expression were suppressed by chronic LiCl pretreatment and the knockdown of TRPC 3. Additionally, cell proliferation was attenuated in TRPC 3 Low cells, compared with the negative control vector‐transfected cell. Conclusions The reduced Ca 2+ mobilization and S100B expression levels following chronic LiCl pretreatment and in TRPC 3 Low cells support the notion that TRPC 3 modulates S100B expression and is the target of the LiCl effect. Downregulation of TRPC 3 may be an important mechanism by which lithium ameliorates pathophysiological intracellular Ca 2+ disturbances as observed in BD , accounting, in part, for its mood‐stabilizing effects.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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".