PMID- 18382462
OWN - NLM
STAT- MEDLINE
DCOM- 20080813
LR  - 20160429
IS  - 1097-6256 (Print)
IS  - 1097-6256 (Linking)
VI  - 11
IP  - 6
DP  - 2008 Jun
TI  - Developmental axon pruning mediated by BDNF-p75NTR-dependent axon degeneration.
PG  - 649-58
LID - 10.1038/nn.2114 [doi]
AB  - The mechanisms that regulate the pruning of mammalian axons are just now being 
      elucidated. Here, we describe a mechanism by which, during developmental 
      sympathetic axon competition, winning axons secrete brain-derived neurotrophic 
      factor (BDNF) in an activity-dependent fashion, which binds to the p75 
      neurotrophin receptor (p75NTR) on losing axons to cause their degeneration and, 
      ultimately, axon pruning. Specifically, we found that pruning of rat and mouse 
      sympathetic axons that project to the eye requires both activity-dependent BDNF 
      and p75NTR. p75NTR and BDNF are also essential for activity-dependent axon 
      pruning in culture, where they mediate pruning by directly causing axon 
      degeneration. p75NTR, which is enriched in losing axons, causes axonal 
      degeneration by suppressing TrkA-mediated signaling that is essential for axonal 
      maintenance. These data provide a mechanism that explains how active axons can 
      eliminate less-active, competing axons during developmental pruning by directly 
      promoting p75NTR-mediated axonal degeneration.
FAU - Singh, Karun K
AU  - Singh KK
AD  - Developmental and Stem Cell Biology, Hospital for Sick Children, 555 University 
      Avenue, Toronto, Canada M5G 1X8.
FAU - Park, Katya J
AU  - Park KJ
FAU - Hong, Elizabeth J
AU  - Hong EJ
FAU - Kramer, Bianca M
AU  - Kramer BM
FAU - Greenberg, Michael E
AU  - Greenberg ME
FAU - Kaplan, David R
AU  - Kaplan DR
FAU - Miller, Freda D
AU  - Miller FD
LA  - eng
GR  - Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080401
PL  - United States
TA  - Nat Neurosci
JT  - Nature neuroscience
JID - 9809671
RN  - 0 (2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Receptor, Nerve Growth Factor)
RN  - 0 (Stilbamidines)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 660YQ98I10 (Potassium Chloride)
RN  - 9012-63-9 (Cholera Toxin)
RN  - 9061-61-4 (Nerve Growth Factor)
SB  - IM
CIN - Nat Neurosci. 2008 Jun;11(6):627-8. PMID: 18506137
MH  - Animals
MH  - Animals, Newborn
MH  - Axons/drug effects/*physiology
MH  - Axotomy/methods
MH  - Brain-Derived Neurotrophic Factor/pharmacology/*physiology
MH  - Cells, Cultured
MH  - Cholera Toxin/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation, Developmental/drug effects/physiology
MH  - Green Fluorescent Proteins/biosynthesis/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Nerve Degeneration/drug therapy/genetics/*physiopathology
MH  - Nerve Growth Factor/pharmacology
MH  - Neurons/cytology
MH  - Potassium Chloride/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Nerve Growth Factor/deficiency/*physiology
MH  - Stilbamidines/metabolism
MH  - Superior Cervical Ganglion/cytology/growth & development
MH  - Visual Pathways/growth & development/metabolism
EDAT- 2008/04/03 09:00
MHDA- 2008/08/14 09:00
CRDT- 2008/04/03 09:00
PHST- 2008/03/13 00:00 [received]
PHST- 2008/03/25 00:00 [accepted]
PHST- 2008/04/03 09:00 [pubmed]
PHST- 2008/08/14 09:00 [medline]
PHST- 2008/04/03 09:00 [entrez]
AID - nn.2114 [pii]
AID - 10.1038/nn.2114 [doi]
PST - ppublish
SO  - Nat Neurosci. 2008 Jun;11(6):649-58. doi: 10.1038/nn.2114. Epub 2008 Apr 1.