Journal
JOURNAL OF NEUROSCIENCE
Volume 26, Issue 30, Pages 7820-7825Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1957-06.2006
Keywords
RNA interference; short hairpin RNA; interferon response; synaptic transmission; dendritic spine; off-target effects
Categories
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Recommended
No Data Available