PMID- 11717413
OWN - NLM
STAT- MEDLINE
DCOM- 20020110
LR  - 20181113
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 98
IP  - 25
DP  - 2001 Dec 4
TI  - Neurotrophins are key mediators of the myelination program in the peripheral 
      nervous system.
PG  - 14661-8
AB  - Although knowledge of the functions of neurotrophins has advanced rapidly in 
      recent years, studies concerning the involvement of neurotrophins in 
      glial-neuronal interactions rarely extend further than their roles in supporting 
      the survival and differentiation of neuronal cells. In this study endogenous 
      brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) were identified 
      in Schwann cell/dorsal root ganglia neuronal cocultures and shown to modulate the 
      myelination program of the peripheral nervous system. The differential expression 
      of BDNF and NT3 were examined and compared with the expression profiles of myelin 
      proteins in the cocultures throughout the myelination process. BDNF levels 
      correlated with active myelin formation, whereas NT3 expression was initially 
      high and then down regulated throughout the proliferation and premyelination 
      periods. Addition of exogenous BDNF enhanced myelination, whereas the removal of 
      the endogenous BDNF by using the BDNF receptor TrkB-Fc fusion protein inhibited 
      the formation of mature myelin internodes. Interestingly, exogenous NT3 
      significantly inhibited myelination, whereas the removal of the endogenous NT3 by 
      using the NT3 receptor TrkC-Fc fusion protein resulted in an enhancement similar 
      to that obtained with the addition of BDNF. In addition, in vivo studies were 
      performed during the development of the mouse sciatic nerve. Subcutaneous 
      injections of BDNF resulted in an enhancement of myelin formation in the sciatic 
      nerve, whereas the removal of the endogenous BDNF dramatically inhibited 
      myelination. Injections of NT3 inhibited myelin formation, and the removal of the 
      endogenous NT3 enhanced myelination. These results demonstrate that BDNF and NT3 
      possess different modulatory roles in the myelination program of the peripheral 
      nervous system and that their mechanisms of action are specific and highly 
      regulated.
FAU - Chan, J R
AU  - Chan JR
AD  - Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 
      94305, USA.
FAU - Cosgaya, J M
AU  - Cosgaya JM
FAU - Wu, Y J
AU  - Wu YJ
FAU - Shooter, E M
AU  - Shooter EM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20011120
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neurotrophin 3)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microscopy, Electron
MH  - Models, Neurological
MH  - Myelin Sheath/*physiology/ultrastructure
MH  - Neurons/physiology/ultrastructure
MH  - Neurotrophin 3/*physiology
MH  - Peripheral Nerves/*growth & development/physiology
MH  - Rats
MH  - Receptor, trkB/physiology
MH  - Recombinant Fusion Proteins/physiology
MH  - Schwann Cells/physiology/ultrastructure
MH  - Sciatic Nerve/growth & development/physiology
PMC - PMC64738
EDAT- 2001/11/22 10:00
MHDA- 2002/01/11 10:01
PMCR- 2002/06/04
CRDT- 2001/11/22 10:00
PHST- 2001/11/22 10:00 [pubmed]
PHST- 2002/01/11 10:01 [medline]
PHST- 2001/11/22 10:00 [entrez]
PHST- 2002/06/04 00:00 [pmc-release]
AID - 251543398 [pii]
AID - 5433 [pii]
AID - 10.1073/pnas.251543398 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14661-8. doi: 10.1073/pnas.251543398. 
      Epub 2001 Nov 20.