Linked Life Data

16870727

Source:http://linkedlifedata.com/resource/pubmed/id/16870727

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
30
pubmed:dateCreated
2006-7-27
pubmed:abstractText
RNA interference (RNAi), which allows selective gene silencing, has been proposed for functional genomic analysis and for the treatment of human disease. However, induction of RNAi in mammalian cells by expression of double-stranded RNA can activate innate antiviral response pathways that perturb off-target gene expression. The activation and functional consequences of these effects in neurons are unknown. We find that expression of subsets of short hairpin RNAs (shRNAs) in rat hippocampal pyramidal neurons can have off-target effects that reduce the complexity of dendritic arbors and trigger the loss of dendritic spines. Morphological changes are accompanied by electrophysiological perturbations in passive membrane properties and a decrease in the number and strength of excitatory and inhibitory synapses. These perturbations depend on the shRNA sequence and are independent of the identity of the targeted protein. Our results indicate that off-target effects of RNAi severely perturb neuronal structure and function and may lead to the functional withdrawal of affected cells from the brain circuitry.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
26
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7820-5
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Retraction of synapses and dendritic spines induced by off-target effects of RNA interference.
pubmed:affiliation
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural