Send to

Choose Destination
Physiol Rep. 2017 Jan;5(1). pii: e13103. doi: 10.14814/phy2.13103.

Chronic TrkB agonist treatment in old age does not mitigate diaphragm neuromuscular dysfunction.

Author information

Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.
Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota.
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota


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 TrkBF616A 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 TrkBF616A 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.


7‐8‐dihydroxyflavone; Brain‐derived neurotrophic factor; Neuromuscular transmission failure; Tropomyosin‐related kinase

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center