Effects of exercise training and TrkB blockade on cardiac function and BDNF-TrkB signaling postmyocardial infarction in rats
Bibliographic record
Abstract
Exercise training is beneficial for preserving cardiac function postmyocardial infarction (post-MI), but the underlying mechanisms are not well understood. We investigated one possible mechanism, brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) signaling, with the TrkB blocker ANA-12 (0.5 mg·kg−1·day−1). Male Wistar rats underwent sham surgery or ligation of the left descending coronary artery. The surviving MI rats were allocated as follows: sedentary MI rats treated with vehicle, exercise-trained MI rats treated with vehicle, and exercise-trained MI rats treated with ANA-12. Exercise training was done 5 days/wk for 4 wk on a motor-driven treadmill. At the end, left ventricular (LV) function was evaluated by echocardiography and a Millar catheter. Mature BDNF and downstream effectors of BDNF-TrkB signaling, Ca2+/calmodulin-dependent protein kinase II (CaMKII), Akt, and AMP-activated protein kinase (AMPK), were assessed in the noninfarct area of the LV by Western blot analysis. Exercise training increased stroke volume and cardiac index and attenuated the decrease in ejection fraction (EF) and increase in LV end-diastolic pressure post-MI. ANA-12 blocked the improvement of EF and attenuated the increases in stroke volume and cardiac index but did not affect LV end-diastolic pressure. Exercise training post-MI prevented decreases in mature BDNF, phosphorylated (p-)CaMKII, p-Akt, and p-AMPKα expression. These effects were all blocked by ANA-12 except for p-AMPKα. In conclusion, the exercise-induced improvement of EF is mediated by the BDNF-TrkB axis and the downstream effectors CaMKII and Akt. BDNF-TrkB signaling appears to contribute to the improvement in systolic function by exercise training. NEW & NOTEWORTHY Exercise training improves ejection fraction and left ventricular end-diastolic pressure (LVEDP) and increases stroke volume and cardiac index in rats postmyocardial infarction (post-MI). The improvement of EF but not LVEDP is mediated by activation of the brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) axis and downstream effectors Ca2+/calmodulin-dependent protein kinase II (CaMKII) and Akt. This suggests that activation of BDNF-TrkB signaling and CaMKII and Akt is a promising target to attenuate progressive cardiac dysfunction post-MI.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".