Linked Life Data

21645877

Source:http://linkedlifedata.com/resource/pubmed/id/21645877

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2011-6-17
pubmed:abstractText
Rac1, a protein of the Rho GTPase subfamily, has been implicated in neuronal and spine development as well as the formation of synapses with appropriate partners. Dendrite and spine abnormalities have been implicated in several psychiatric disorders such as Fragile X syndrome, where neurons show a high density of long, thin, and immature dendritic spines. Although abnormalities in dendrites and spines have been correlated with impaired cognitive abilities in mental retardation, the causes of these malformations are not yet well understood. Fragile X syndrome is the most common type of inherited mental retardation caused by the absence of FMRP protein, a RNA-binding protein implicated in the regulation of mRNA translation and transport, leading to protein synthesis. We suggest that FMRP might act as a negative regulator on the synthesis of Rac1. Maintaining an optimal level of Rac1 and facilitating the reorganization of the cytoskeleton likely leads to normal neuronal morphology during activity-dependent plasticity. In our study, we first demonstrated that Rac1 is not only associated but necessary for normal spine development and long-term synaptic plasticity. We further showed that, in Fmr1 knockout mice, lack of FMRP induces an overactivation of Rac1 in the mouse brain and other organs that have been shown to be altered in Fragile X syndrome. In those animals, pharmacological manipulation of Rac1 partially reverses their altered long-term plasticity. Thus, regulation of Rac1 may provide a functional link among deficient neuronal morphology, aberrant synaptic plasticity and cognition impairment in Fragile X syndrome.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1872-6240
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
1399
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
79-95
pubmed:meshHeading
pubmed-meshheading:21645877-Aminoquinolines, pubmed-meshheading:21645877-Analysis of Variance, pubmed-meshheading:21645877-Animals, pubmed-meshheading:21645877-Brain, pubmed-meshheading:21645877-Dendrites, pubmed-meshheading:21645877-Dendritic Spines, pubmed-meshheading:21645877-Disease Models, Animal, pubmed-meshheading:21645877-Electric Stimulation, pubmed-meshheading:21645877-Excitatory Amino Acid Antagonists, pubmed-meshheading:21645877-Excitatory Postsynaptic Potentials, pubmed-meshheading:21645877-Fragile X Mental Retardation Protein, pubmed-meshheading:21645877-Fragile X Syndrome, pubmed-meshheading:21645877-Gene Expression Regulation, pubmed-meshheading:21645877-Methoxyhydroxyphenylglycol, pubmed-meshheading:21645877-Mice, pubmed-meshheading:21645877-Mice, Inbred C57BL, pubmed-meshheading:21645877-Mice, Transgenic, pubmed-meshheading:21645877-Neurons, pubmed-meshheading:21645877-Patch-Clamp Techniques, pubmed-meshheading:21645877-Pyrimidines, pubmed-meshheading:21645877-Signal Transduction, pubmed-meshheading:21645877-Silver Staining, pubmed-meshheading:21645877-Synapses, pubmed-meshheading:21645877-rac1 GTP-Binding Protein
pubmed:year
2011
pubmed:articleTitle
Modulation of dendritic spines and synaptic function by Rac1: a possible link to Fragile X syndrome pathology.
pubmed:affiliation
Department of Pharmacological and Pharmaceutical Sciences, University of Houston, 521 Science and Research Bldg 2, Houston, TX 77204, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural