PMID- 12771168
OWN - NLM
STAT- MEDLINE
DCOM- 20031104
LR  - 20190607
IS  - 0022-0949 (Print)
IS  - 0022-0949 (Linking)
VI  - 206
IP  - Pt 13
DP  - 2003 Jul
TI  - Neurotrophin 4/5 is required for the normal development of the slow muscle fiber 
      phenotype in the rat soleus.
PG  - 2191-200
AB  - During normal postnatal development, rat soleus (SOL) muscle fibers undergo a 
      dramatic fast-to-slow myosin heavy chain (MyHC) isoform transformation. We 
      exploited this phenomenon to evaluate the role of neurotrophin 4/5 (NT-4/5) in 
      the regulation of muscle fiber phenotype. Intramuscular injections of recombinant 
      NT-4/5 into the SOL muscle of rat neonates significantly accelerated the normal 
      fast-to-slow MyHC isoform transformation. Sequestration of endogenous NT-4/5 with 
      TrkB-IgG prevented this transformation from occurring. Administration of the 
      other TrkB ligand, brain-derived neurotrophic factor (BDNF), did not affect the 
      normal course of the MyHC isoform transformation in this muscle, indicating that 
      the observed effect is NT-4/5 specific. Botulinum toxin blockade of synaptic 
      transmission significantly disrupted the normal fast-to-slow MyHC isoform switch. 
      Because administration of NT-4/5 to paralyzed muscles failed to restore the 
      normal course of this MyHC transformation, we believe that the effect of NT-4/5 
      is not directly on the muscle fibers but that it probably activates or forms a 
      type of retrograde signal to motoneurons. The developmental upregulation of 
      NT-4/5 mRNA in rat SOL muscle fibers occurred earlier than the upregulation of 
      MyHC I/b mRNA associated with muscle fiber transformation. This timing is 
      consistent with the idea that NT-4/5 is involved in early events that lead to the 
      upregulation of the slow MyHC isoform in this muscle.
FAU - Carrasco, Dario I
AU  - Carrasco DI
AD  - Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 
      30322, USA. dcarras@emory.edu
FAU - English, Arthur W
AU  - English AW
LA  - eng
GR  - AR08564/AR/NIAMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Exp Biol
JT  - The Journal of experimental biology
JID - 0243705
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (DNA Primers)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Protein Isoforms)
RN  - 145172-44-7 (neurotrophin 5)
RN  - EC 3.4.24.69 (Botulinum Toxins)
RN  - EC 3.6.4.1 (Myosin Heavy Chains)
RN  - P658DCA9XD (neurotrophin 4)
SB  - IM
MH  - Animals
MH  - Botulinum Toxins/pharmacology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - DNA Primers
MH  - Immunohistochemistry
MH  - Models, Biological
MH  - Muscle Fibers, Slow-Twitch/*physiology
MH  - Muscle, Skeletal/*growth & development
MH  - Myosin Heavy Chains/physiology
MH  - Nerve Growth Factors/*physiology
MH  - Neuromuscular Blockade
MH  - Protein Isoforms/drug effects/physiology
MH  - Rats/*growth & development/physiology
MH  - Up-Regulation/physiology
EDAT- 2003/05/29 05:00
MHDA- 2003/11/05 05:00
CRDT- 2003/05/29 05:00
PHST- 2003/05/29 05:00 [pubmed]
PHST- 2003/11/05 05:00 [medline]
PHST- 2003/05/29 05:00 [entrez]
AID - 10.1242/jeb.00412 [doi]
PST - ppublish
SO  - J Exp Biol. 2003 Jul;206(Pt 13):2191-200. doi: 10.1242/jeb.00412.