PMID- 23821558
OWN - NLM
STAT- MEDLINE
DCOM- 20140411
LR  - 20231213
IS  - 1932-846X (Electronic)
IS  - 1932-8451 (Linking)
VI  - 73
IP  - 10
DP  - 2013 Oct
TI  - Neuropeptide orphanin FQ inhibits dendritic morphogenesis through activation of 
      RhoA.
PG  - 769-84
LID - 10.1002/dneu.22101 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) plays a facilitatory role in neuronal 
      development and promotion of differentiation. Mechanisms that oppose BDNF's 
      stimulatory effects create balance and regulate dendritic growth. However, these 
      mechanisms have not been studied. We have focused our studies on the BDNF-induced 
      neuropeptide OrphaninFQ/ Nociceptin (OFQ); while BDNF is known to enhance 
      synaptic activity, OFQ has opposite effects on activity, learning, and memory. We 
      have now examined whether OFQ provides a balance to the stimulatory effects of 
      BDNF on neuronal differentiation in the hippocampus. Golgi staining in OFQ 
      knockout (KO) mice revealed an increase in primary dendrite length as well as 
      spine density, suggesting that endogenous OFQ inhibits dendritic morphology. We 
      have also used cultured hippocampal neurons to demonstrate that exogenous OFQ has 
      an inhibitory effect on dendritic growth and that the neuropeptide alters the 
      response to BDNF when pre-administered. To determine if BDNF and OFQ act in a 
      feedback loop, we inhibited the actions of the BDNF and OFQ receptors, TrkB and 
      NOP using ANA-12 and NOP KO mice respectively but our data suggest that the two 
      factors do not act in a negative feedback loop. We found that the inhibition of 
      dendritic morphology induced by OFQ is via enhanced RhoA activity. Finally, we 
      have evidence that RhoA activation is required for the inhibitory effects of OFQ 
      on dendritic morphology. Our results reveal basic mechanisms by which neurons not 
      only regulate the formation of proper dendritic growth during development but 
      also control plasticity in the mature nervous system.
CI  - Copyright (c) 2013 Wiley Periodicals, Inc.
FAU - Alder, Janet
AU  - Alder J
AD  - Department of Neuroscience and Cell Biology, University of Medicine and Dentistry 
      of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey.
FAU - Kallman, Seth
AU  - Kallman S
FAU - Palmieri, Alicia
AU  - Palmieri A
FAU - Khadim, Farah
AU  - Khadim F
FAU - Ayer, Jennifer J
AU  - Ayer JJ
FAU - Kumar, Sujata
AU  - Kumar S
FAU - Tsung, Katherine
AU  - Tsung K
FAU - Grinberg, Ilya
AU  - Grinberg I
FAU - Thakker-Varia, Smita
AU  - Thakker-Varia S
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130820
PL  - United States
TA  - Dev Neurobiol
JT  - Developmental neurobiology
JID - 101300215
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuropeptides)
RN  - 0 (Opioid Peptides)
RN  - 0 (Receptors, Opioid)
RN  - EC 3.6.5.2 (RhoA protein, mouse)
RN  - EC 3.6.5.2 (rho GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
RN  - 0 (Nociceptin Receptor)
RN  - 0 (Oprl1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Dendrites/*drug effects/metabolism
MH  - Male
MH  - Memory/physiology
MH  - Mice
MH  - Mice, 129 Strain
MH  - Mice, Knockout
MH  - Neurogenesis/physiology
MH  - Neurons/drug effects/metabolism
MH  - Neuropeptides/*pharmacology
MH  - Opioid Peptides/*pharmacology
MH  - Receptors, Opioid/metabolism
MH  - rho GTP-Binding Proteins/genetics/*metabolism
MH  - rhoA GTP-Binding Protein
MH  - Nociceptin Receptor
MH  - Nociceptin
OTO - NOTNLM
OT  - RhoA
OT  - brain-derived neurotrophic factor
OT  - dendrite
OT  - neuropeptide
OT  - orphanin FQ/nociceptin
EDAT- 2013/07/04 06:00
MHDA- 2014/04/12 06:00
CRDT- 2013/07/04 06:00
PHST- 2013/03/04 00:00 [received]
PHST- 2013/06/20 00:00 [revised]
PHST- 2013/06/21 00:00 [accepted]
PHST- 2013/07/04 06:00 [entrez]
PHST- 2013/07/04 06:00 [pubmed]
PHST- 2014/04/12 06:00 [medline]
AID - 10.1002/dneu.22101 [doi]
PST - ppublish
SO  - Dev Neurobiol. 2013 Oct;73(10):769-84. doi: 10.1002/dneu.22101. Epub 2013 Aug 20.