PMID- 16878402
OWN - NLM
STAT- MEDLINE
DCOM- 20060905
LR  - 20191110
IS  - 0334-1763 (Print)
IS  - 0334-1763 (Linking)
VI  - 17
IP  - 3
DP  - 2006
TI  - Nitric oxide and synaptic dynamics in the adult brain: physiopathological 
      aspects.
PG  - 309-57
AB  - The adult brain retains the capacity to rewire mature neural circuits in response 
      to environmental changes, brain damage or sensory and motor experiences. Two 
      plastic processes, synaptic remodeling and neurogenesis, have been the subject of 
      numerous studies due to their involvement in the maturation of the nervous 
      system, their prevalence and re-activation in adulthood, and therapeutic 
      relevance. However, most of the research looking for the mechanistic and 
      molecular events underlying synaptogenic phenomena has been focused on the 
      extensive synaptic reorganization occurring in the developing brain. In this 
      stage, a vast number of synapses are initially established, which subsequently 
      undergo a process of activity-dependent refinement guided by target-derived 
      signals that act as synaptotoxins or synaptotrophins, promoting either loss or 
      consolidation of pre-existing synaptic contacts, respectively. Nitric oxide (NO), 
      an autocrine and/or paracrine-acting gaseous molecule synthesized in an 
      activity-dependent manner, has ambivalent actions. It can act by mediating 
      synapse formation, segregation of afferent inputs, or growth cone collapse and 
      retraction in immature neural systems. Nevertheless, little information exists 
      about the role of this ambiguous molecule in synaptic plasticity processes 
      occurring in the adult brain. Suitable conditions for elucidating the role of NO 
      in adult synaptic rearrangement include physiopathological conditions, such as 
      peripheral nerve injury. We have recently developed a crush lesion model of the 
      XIIth nerve that induces a pronounced stripping of excitatory synaptic boutons 
      from the cell bodies of hypoglossal motoneurons. The decline in synaptic coverage 
      was concomitant with de novo expression of the neuronal isoform of NO synthase in 
      motoneurons. We have demonstrated a synaptotoxic action of NO mediating synaptic 
      withdrawal and preventing synapse formation by cyclic GMP (cGMP)-dependent and, 
      probably, S-nitrosylation-mediated mechanisms, respectively. This action possibly 
      involves the participation of other signaling molecules working together with NO. 
      Brain-derived neurotrophic factor (BDNF), a target-derived synaptotrophin 
      synthesized and released postsynaptically in an activity-dependent form, is a 
      potential candidate for effecting such a concerted action. Several items of 
      evidence support an interrelationship between NO and BDNF in the regulation of 
      synaptic remodeling processes in adulthood: i) BDNF and its receptor TrkB are 
      expressed by motoneurons and upregulated by axonal injury; ii) they promote axon 
      arborization and synaptic formation, and modulate the structural dynamics of 
      excitatory synapses; iii) NO and BDNF each control the production and activity of 
      the other at the level of individual synapses; iv) the NO/cGMP pathway inhibits 
      BDNF secretion; and finally, v) BDNF protects F-actin from depolymerization by 
      NO, thus preventing the collapsing and retracting effects of NO on growth cones. 
      Therefore, we propose a mechanism of action in which the NO/BDNF ratio regulates 
      synapse dynamics after peripheral nerve lesion. This hypothesis also raises the 
      possibility that variations in this NO/BDNF balance constitute a common hallmark 
      leading to synapse loss in the progression of diverse neurodegenerative diseases 
      such as amyotrophic lateral sclerosis, Alzheimer's and Parkinson's diseases.
FAU - Moreno-Lopez, Bernardo
AU  - Moreno-Lopez B
AD  - Area de Fisiologia, Facultad de Medicina, Universidad de Cadiz, Cadiz, Spain. 
      bernardo.moreno@uca.es
FAU - Gonzalez-Forero, David
AU  - Gonzalez-Forero D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Germany
TA  - Rev Neurosci
JT  - Reviews in the neurosciences
JID - 8711016
RN  - 0 (Nerve Tissue Proteins)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Animals
MH  - Brain/*enzymology/*physiopathology
MH  - Humans
MH  - Nerve Tissue Proteins/metabolism
MH  - Neurodegenerative Diseases/enzymology/physiopathology
MH  - Nitric Oxide/*metabolism
MH  - *Nonlinear Dynamics
MH  - Synapses/*physiology
RF  - 423
EDAT- 2006/08/02 09:00
MHDA- 2006/09/06 09:00
CRDT- 2006/08/02 09:00
PHST- 2006/08/02 09:00 [pubmed]
PHST- 2006/09/06 09:00 [medline]
PHST- 2006/08/02 09:00 [entrez]
AID - 10.1515/revneuro.2006.17.3.309 [doi]
PST - ppublish
SO  - Rev Neurosci. 2006;17(3):309-57. doi: 10.1515/revneuro.2006.17.3.309.