PMID- 10662836
OWN - NLM
STAT- MEDLINE
DCOM- 20000225
LR  - 20191023
IS  - 0270-6474 (Print)
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Linking)
VI  - 20
IP  - 4
DP  - 2000 Feb 15
TI  - Stabilization of growing retinal axons by the combined signaling of nitric oxide 
      and brain-derived neurotrophic factor.
PG  - 1458-69
AB  - The pattern of axonal projections early in the development of the nervous system 
      lacks the precision present in the adult. During a developmental process of 
      refinement, mistargeted projections are eliminated while correct projections are 
      retained. Previous studies suggest that during development nitric oxide (NO) is 
      involved in the elimination of mistargeted retinal axons, whereas brain-derived 
      neurotrophic factor (BDNF) may stabilize retinal axon arbors. It is unclear 
      whether these neuromodulators interact. This study showed that NO induced growth 
      cone collapse and retraction of developing retinal axons. This effect was not 
      attributable to NO-induced neurotoxicity. BDNF protected growth cones and axons 
      from the effects of NO. This effect was specific to BDNF, because neither nerve 
      growth factor (NGF) nor neurotrophin-3 (NT-3) prevented NO-induced growth cone 
      collapse and axon retraction. Exposure to both BDNF and NO, but not either factor 
      alone, stabilized growth cones and axons. Stabilized axons exhibited minimal 
      retraction or extension. This response appears to be a new axon "state" and not 
      simply a partial amelioration of the effect of NO, because lower doses of BDNF or 
      NO allowed axon extension. Furthermore, BDNF/NO-induced growth cone stabilization 
      correlated with the appearance of a cytochalasin D-resistant population of actin 
      filaments. BDNF protection from NO likely was mediated locally at the level of 
      the growth cone, because growth cones or individual filopodia in contact with 
      BDNF-coated beads were protected from NO-induced collapse. These findings suggest 
      a cellular mechanism by which some axonal connections are stabilized and some are 
      eliminated during development.
FAU - Ernst, A F
AU  - Ernst AF
AD  - Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 
      55455, USA.
FAU - Gallo, G
AU  - Gallo G
FAU - Letourneau, P C
AU  - Letourneau PC
FAU - McLoon, S C
AU  - McLoon SC
LA  - eng
GR  - R01 HD019950/HD/NICHD NIH HHS/United States
GR  - EY11926/EY/NEI NIH HHS/United States
GR  - HD19950/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamine)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Hydrazines)
RN  - 0 (Neurotrophin 3)
RN  - 0 (Nitric Oxide Donors)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 5O5U71P6VQ (linsidomine)
RN  - D46583G77X (Molsidomine)
SB  - IM
MH  - Animals
MH  - Axons/drug effects/*physiology/ultrastructure
MH  - Brain-Derived Neurotrophic Factor/pharmacology/*physiology
MH  - Cells, Cultured
MH  - Chick Embryo
MH  - Ganglia, Spinal/cytology/embryology/*physiology
MH  - Heart/embryology
MH  - Hydrazines/pharmacology
MH  - Molsidomine/analogs & derivatives/pharmacology
MH  - Neurons/cytology/drug effects/*physiology
MH  - Neurotrophin 3/pharmacology
MH  - Nitric Oxide/*physiology
MH  - Nitric Oxide Donors/*pharmacology
MH  - Organ Culture Techniques
MH  - Retina/cytology/embryology/*physiology
MH  - Signal Transduction
MH  - Visual Pathways/physiology
PMC - PMC6772364
EDAT- 2000/02/09 09:00
MHDA- 2000/03/04 09:00
PMCR- 2000/08/15
CRDT- 2000/02/09 09:00
PHST- 2000/02/09 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 2000/02/09 09:00 [entrez]
PHST- 2000/08/15 00:00 [pmc-release]
AID - 3907 [pii]
AID - 10.1523/JNEUROSCI.20-04-01458.2000 [doi]
PST - ppublish
SO  - J Neurosci. 2000 Feb 15;20(4):1458-69. doi: 10.1523/JNEUROSCI.20-04-01458.2000.