Retraction of Synapses and Dendritic Spines Induced by Off-target Effects of Rna Interference.
From: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publish Date: Jul 2006
- ISSN: 1529-2401
- Volume: 26
- Issue: 30
- Pages: 7820-5
- Medium: Internet
- Language: English
- Citation (JAMA): Alvarez Veronica A, Ridenour Dennis A, Sabatini Bernardo L, et al. Retraction of Synapses and Dendritic Spines Induced by Off-target Effects of Rna Interference.. J. Neurosci. Jul 2006;26:7820-5
Abstract
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.
Mesh Headings (Keywords): Adaptation, Physiological, Animals, Cells, Cultured, Dendrites, Hippocampus, Nerve Tissue Proteins, RNA Interference, Rats, Rats, Sprague-Dawley, Synapses
Check for Full Text / PubMed Unique Identifier (PMID): 16870727
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.