期刊
JOURNAL OF PHYSIOLOGY-LONDON
卷 593, 期 2, 页码 431-440出版社
WILEY-BLACKWELL
DOI: 10.1113/jphysiol.2014.282244
关键词
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资金
- National Institute of Health [R01-AG044615, T32-HL105355]
- Mayo Clinic
The age-related mechanisms underlying sarcopenia are largely unknown. We hypothesize that age-related neuromuscular changes depend on brain-derived neurotrophic factor (BDNF) acting through the tropomyosin-related kinase receptor B (TrkB). Maximal specific force and neuromuscular transmission failure were assessed at 6, 18 and 24months following control, BDNF or phosphoprotein phosphatase 1 derivative (1NMPP1) treatment in male TrkB(F616A) mice. Phosphoprotein phosphatase-1 derivatives such as 1NMPP1 inhibit TrkB kinase activity as a result of this single amino acid mutation in the ATP binding domain. Maximal twitch and isometric tetanic force were reduced at 24months compared to 6 and 18months (P<0.001). Neuromuscular transmission failure significantly increased at 18 and 24months compared to 6months (agextreatment interaction: P<0.001). Neuromuscular transmission was improved following BDNF at 6 and 18months and was impaired only at 6months following 1NMPP1 treatment. Age and inhibition of TrkB kinase activity had similar effects on neuromuscular transmission failure, supporting a critical role for BDNF/TrkB signalling on neuromuscular changes in ageing. These results suggest that an age-related loss of endogenous BDNF precedes reductions in TrkB kinase activity in the diaphragm muscle.
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