# The Role of Myocardial BDNF signaling in Myocardial physiology and myocardial response to pathological stress

> **NIH NIH K08** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $124,686

## Abstract

Project summary/Abstract
 Brain-derived neurotrophic factor (BDNF) is a neurotrophin that regulates energy homeostasis,
mitochondrial bioenergetics and mediates exercise-induced neurogenesis in the brain. Both BDNF and its
receptor Tropomyosin related kinase receptor B (TrkB) are present in the myocardium. However, the role of
BDNF/TrkB signaling in myocardial physiology and the myocardial response to pathological stress is largely
unknown. My recent first author publication in PNAS found that constitutive myocardial BDNF/TrkB signaling is
required for normal cardiac contraction and relaxation. In new preliminary data, we found exercise induced BDNF
expression in the heart, whereas BDNF expression was decreased in myocardium from human heart failure
patients and mouse heart failure models. The mice with transgenic myocardial BDNF over-expression showed
preserved cardiac function against pressure overload induced by transaortic constriction (TAC). Conversely,
cardiac specific TrkB-/- mice (cTrkB-/-) displayed accelerated heart failure progression under pressure overload.
Moreover, a small molecule TrkB agonist prevented progression of heart failure in mice, suggesting the
BDNF/TrkB pathway could be a novel therapeutic target. Importantly, we found the expression of Peroxisome
proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), a master regulator of mitochondrial
biogenesis and mitochondrial respiratory function, was decreased in pressure overload in mice, while over-
expression of BDNF restored the impaired PGC1α expression in the stressed hearts. In addition, we also found
that the expression of myofibrillar isoform of creatine kinase (CK) was decreased in myocardium after TAC, and
recovered in cBDNF-tg mice. CK plays a critical role in energy reservation by ATP regeneration through
conversion of creatine phosphate (pCr) and ADP. Thus I will test the hypothesis that BDNF/TrkB activation is
critical for exercise physiology and protects against pathological stress by improving cardiac bio-energetics, via
PGC1α dependent mitochondrial function enhancement and CK mediated ATP regeneration. This hypothesis
will be addressed in three specific aims leveraging our novel transgenic mice models: 1) Determine the
importance of myocardial BDNF/TrkB on exercise capacity and exercise induced adaptive response; 2) Test
whether myocardial BDNF/TrkB signaling protects against pressure overload by activating PGC1α; 3) Test
whether myocardial BDNF/TrkB signaling protects against pressure overload by augmenting creatine kinase
mediated ATP regeneration

## Key facts

- **NIH application ID:** 9966018
- **Project number:** 5K08HL130604-06
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Ning Feng
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $124,686
- **Award type:** 5
- **Project period:** 2018-01-15 → 2022-03-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9966018

## Citation

> US National Institutes of Health, RePORTER application 9966018, The Role of Myocardial BDNF signaling in Myocardial physiology and myocardial response to pathological stress (5K08HL130604-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9966018. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*