PMID- 25630263
OWN - NLM
STAT- MEDLINE
DCOM- 20151014
LR  - 20181113
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Print)
IS  - 0022-3751 (Linking)
VI  - 593
IP  - 2
DP  - 2015 Jan 15
TI  - Ageing and neurotrophic signalling effects on diaphragm neuromuscular function.
PG  - 431-40
LID - 10.1113/jphysiol.2014.282244 [doi]
AB  - 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 24 months 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 24 months 
      compared to 6 and 18 months (P < 0.001). Neuromuscular transmission failure 
      significantly increased at 18 and 24 months compared to 6 months (age x treatment 
      interaction: P < 0.001). Neuromuscular transmission was improved following BDNF 
      at 6 and 18 months and was impaired only at 6 months 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.
CI  - (c) 2014 The Authors. The Journal of Physiology (c) 2014 The Physiological Society.
FAU - Greising, Sarah M
AU  - Greising SM
AD  - Department of Physiology and Biomedical Engineering, Mayo Clinic College of 
      Medicine, Rochester, MN 55905, USA.
FAU - Ermilov, Leonid G
AU  - Ermilov LG
FAU - Sieck, Gary C
AU  - Sieck GC
FAU - Mantilla, Carlos B
AU  - Mantilla CB
LA  - eng
GR  - R01 AG044615/AG/NIA NIH HHS/United States
GR  - T32 HL105355/HL/NHLBI NIH HHS/United States
GR  - R01-AG044615/AG/NIA NIH HHS/United States
GR  - T32-HL105355/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20141201
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (1NMPP1 compound)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyrimidines)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Aging/*metabolism/physiology
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism/*pharmacology
MH  - Diaphragm/drug effects/growth & development/*metabolism/physiology
MH  - Male
MH  - Mice
MH  - *Muscle Contraction
MH  - Mutation
MH  - Pyrazoles/pharmacology
MH  - Pyrimidines/pharmacology
MH  - Receptor, trkB/genetics/metabolism
MH  - *Signal Transduction
PMC - PMC4303387
EDAT- 2015/01/30 06:00
MHDA- 2015/10/16 06:00
PMCR- 2016/01/15
CRDT- 2015/01/30 06:00
PHST- 2014/08/08 00:00 [received]
PHST- 2014/10/23 00:00 [accepted]
PHST- 2015/01/30 06:00 [entrez]
PHST- 2015/01/30 06:00 [pubmed]
PHST- 2015/10/16 06:00 [medline]
PHST- 2016/01/15 00:00 [pmc-release]
AID - 10.1113/jphysiol.2014.282244 [doi]
PST - ppublish
SO  - J Physiol. 2015 Jan 15;593(2):431-40. doi: 10.1113/jphysiol.2014.282244. Epub 
      2014 Dec 1.