Abstract
Previously, we found that brain-derived neurotrophic factor (BDNF) signaling through the high-affinity tropomyosin-related kinase receptor subtype B (TrkB) enhances neuromuscular transmission in the diaphragm muscle. However, there is an age-related loss of this effect of BDNF/TrkB signaling that may contribute to diaphragm muscle sarcopenia (atrophy and force loss). We hypothesized that chronic treatment with 7,8-dihydroxyflavone (7,8-DHF), a small molecule BDNF analog and TrkB agonist, will mitigate age-related diaphragm neuromuscular transmission failure and sarcopenia in old mice. Adult male TrkBF 616A mice (n = 32) were randomized to the following 6-month treatment groups: vehicle-control, 7,8-DHF, and 7,8-DHF and 1NMPP1 (an inhibitor of TrkB kinase activity in TrkBF 616A mice) cotreatment, beginning at 18 months of age. At 24 months of age, diaphragm neuromuscular transmission failure, muscle-specific force, and fiber cross-sectional areas were compared across treatment groups. The results did not support our hypothesis in that chronic 7,8-DHF treatment did not improve diaphragm neuromuscular transmission or mitigate diaphragm muscle sarcopenia. Taken together, these results do not exclude a role for BDNF/TrkB signaling in aging-related changes in the diaphragm muscle, but they do not support the use of 7,8-DHF as a therapeutic agent to mitigate age-related neuromuscular dysfunction.
Original language | English (US) |
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Article number | e13103 |
Journal | Physiological Reports |
Volume | 5 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2017 |
Bibliographical note
Publisher Copyright:© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
Keywords
- 7-8-dihydroxyflavone
- Brain-derived neurotrophic factor
- Neuromuscular transmission failure
- Tropomyosin-related kinase
PubMed: MeSH publication types
- Journal Article