Effects of Exercise Training and TrkB blockade on Cardiac BDNF‐TrkB signaling post Myocardial Infarction in Rats
Bibliographic record
Abstract
Purpose Exercise training post myocardial infarction (MI) is beneficial for preserving cardiac function, but underlying mechanisms are still unclear. Exercise increases brain‐derived neurotrophic factor (BDNF) in the non‐infarct area of the left ventricle (LV) with an improvement of ejection fraction (EF) and LV end‐diastolic pressure (LVEDP). Whether these effects are mediated by downstream pathways of BDNF via its binding receptor tropomyosin‐related kinase B receptor (TrkB) has not yet been assessed. Therefore, impact of exercise training post MI on cardiac function and one of downstream effectors of BDNF‐TrkB signaling, Ca 2+ /calmodulin dependent protein kinase II (CaMKII), were investigated in exercising rats treated with vehicle or TrkB blocker, ANA‐12. Methods After sham surgery (n=10) or ligation of coronary artery, surviving MI rats were divided into 3 groups: sedentary MI with vehicle (Sed‐MI‐Veh, n=17), exercise MI with vehicle (ExT‐MI‐Veh, n=17) and exercise MI with ANA‐12 (ExT‐MI‐ANA‐12, n=7). Exercise training was done for 4 weeks (5 days/week) on a motor‐driven treadmill with or without ANA‐12 (0.5 mg/kg). At the end, LV function was evaluated by echocardiography and Millar catheter, and mature BDNF (mBDNF), phospho‐CaMKII (p‐CaMKII) and CaMKII (pan) levels were assessed in the non‐infarct area of the LV by Western blotting. Results MI size was similar among the MI groups. ExT‐MI‐Veh showed higher EF compared to Sed‐MI‐Veh (63 ± 2 vs. 54 ± 2%, ExT‐MI‐Veh vs. Sed‐MI‐Veh). Exercise‐induced improvement of EF was inhibited by ANA‐12 (56 ± 2%). LVEDP was significantly lower in exercise MI groups (11.6 ± 0.9 and 12.8 ± 1.6 mmHg, Veh and ANA‐12) compared to Sed‐MI‐Veh (18.4 ± 0.9 mmHg). After MI, p‐CaMKII and p‐CaMKII/CaMKII (pan) were significantly decreased (0.6 ± 0.04 and 0.5 ± 0.1, fold of Sham, respectively). Exercise increased mBDNF (0.9 ± 0.1 vs. 0.7 ± 0.1 vs. fold of Sham, ExT‐MI‐Veh vs. Sed‐MI‐Veh) and p‐CaMKII (0.8 ± 0.1, fold of Sham). ANA‐12 prevented exercise‐induced increases in mBDNF (0.6 ± 0.1, fold of Sham) and p‐CaMKII (0.6 ± 0.1, fold of Sham). Conclusions : Exercise post MI increases EF and decreases LVEDP, but TrkB blockade only inhibits the improvement of EF, but not of LVEDP. Exercise increases mBDNF and p‐CaMKII in the non‐infarct area of the LV, which are attenuated by ANA‐12. This indicates that exercise‐induced improvement of EF is mediated by TrkB and downstream effector CaMKII, and BDNF‐TrkB signaling may be mainly associated with improvement in systolic function by exercise training. Support or Funding Information FRN:MOP‐136923 from the Canadian Institutes of Health Research. Department of Cellular and Molecular Medicine, University of Ottawa This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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 | 0.000 |
| 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 | 0.000 |
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".