The role of ATP and P2X purinoreceptor 7 in the pathogenesis of cerebral tau
Bibliographic record
Abstract
The tauopathies are a group of neurodegenerative diseases characterized by abnormal deposition of hyperphosphorylated-tau. The pathogenesis of these changes remains uncertain. In chronic traumatic encephalopathy, tauopathy is hypothesized to occur after repeated mild traumatic brain injury (TBI). Post-traumatic extracellular ATP release and signalling via the P2X purinoceptor 7 (P2RX7) has been shown to be important in mediating pathological changes in TBI. We hypothesized that ATP-P2RX7 is involved in the development of tauopathy. We injected ATP analogue bzATP or vehicle intraventricularly into C57BL/6 mice, pre-treated with either intraperitoneal P2RX7 antagonist Brilliant Blue G (BBG) or vehicle. At 2 weeks and 3 months, behavioural change was assessed with the tail suspension test, accelerating rotatrod, and fear conditioning; mice were then sacrificed for immunohistochemistry and western blot. We observed increased immobile time in the tail suspension test for mice treated with bzATP at 3 months. Similarly, for rotarod, mice treated with bzATP showed poorer performance at 3 months. These effects were diminished by BBG pre-treatment. Fear conditioning, however, did not demonstrate a significant difference between groups. Immunohistochemical staining for GFAP showed increased intensity at both 2 weeks and 3 months for bzATP-treated mice compared to those pre-treated with BBG. Levels of phosphorylated tau (AT8) were increased in bzATP-treated mice compared to controls. In summary, ATP-P2RX7-mediated mechanisms may play a role in the development of behavioural deficits and tauopathy.
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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 | 0.001 | 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".