ArticleProceedings of the National Academy of Sciences of the United States of America2004
Neurochemical and behavioral consequences of widespread gene knockdown in the adult mouse brain by using nonviral RNA interference.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
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Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 210 citations in OpenAlex.
- Systematic Review of Genetic Substrate Reduction Therapy in Lysosomal Storage Diseases: Opportunities, Challenges and Delivery Systems.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Pooled it
- MambaCAttnGCN+: a comprehensive framework integrating MambaTextCNN, cross-attention and graph convolution network for piRNA-disease association prediction.Scientific reports · 2025Article
- CREB-Binding Protein Regulates Cocaine- and Amphetamine-Regulated Transcript Peptide Expression in the Lateral Hypothalamus: Implication in Reward and Reinforcement.Molecular neurobiology · 2025Article
- Breaking Barriers in Huntington's Disease Therapy: Focused Ultrasound for Targeted Drug Delivery.Neurochemical research · 2025Review
- Databases and computational methods for the identification of piRNA-related molecules: A survey.Computational and structural biotechnology journal · 2024Review
- Dopamine Transporter Deficient Rodents: Perspectives and Limitations for Neuroscience.Biomolecules · 2023Review
- Acute Neurotoxicity of Antisense Oligonucleotides After Intracerebroventricular Injection Into Mouse Brain Can Be Predicted from Sequence Features.Nucleic acid therapeutics · 2022Article
- Non-Viral Delivery of RNA Gene Therapy to the Central Nervous System.Pharmaceutics · 2022Review
- Review of rodent models of attention deficit hyperactivity disorder.Neuroscience and biobehavioral reviews · 2022Review
- Cellular Targeting of Oligonucleotides by Conjugation with Small Molecules.Molecules (Basel, Switzerland) · 2020Review
- A Pediatric Review of Facioscapulohumeral Muscular Dystrophy.Journal of pediatric neurology : JPN · 2018Article
- Dopamine transporter mutant animals: a translational perspective.Journal of neurogenetics · 2016Review
- Hydrophobically Modified siRNAs Silence Huntingtin mRNA in Primary Neurons and Mouse Brain.Molecular therapy. Nucleic acids · 2015Article
- Article
- Epigenetic targets for novel therapies of lung diseases.Pharmacology & therapeutics · 2015Review
- NLRP1 inflammasome is activated in patients with medial temporal lobe epilepsy and contributes to neuronal pyroptosis in amygdala kindling-induced rat model.Journal of neuroinflammation · 2015Article
- Amyloid-β induces NLRP1-dependent neuronal pyroptosis in models of Alzheimer's disease.Cell death & disease · 2014Article
- Morpholino treatment improves muscle function and pathology of Pitx1 transgenic mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Lipid nanoparticles for short interfering RNA delivery.Advances in genetics · 2014Review
- Early-life stress induces persistent alterations in 5-HT1A receptor and serotonin transporter mRNA expression in the adult rat brain.Frontiers in molecular neuroscience · 2014Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene expression analysis implicates an increasing number of novel genes in the brain as potential targets for the treatment of neurological and psychiatric disorders. Frequently, these genes are ubiquitously expressed in the brain and, thus, may contribute to a pathophysiological state through actions in several brain nuclei. Current strategies employing genetically modified animals for in vivo validation of such targets are time-consuming and often limited by developmental adaptations. Somatic gene manipulation using viral-mediated RNA interference (RNAi) has emerged recently, although restricting the target validation to specific brain nuclei. We investigated whether nonviral infusion of short interfering RNA (siRNA) into the ventricular system would enable a sequence-specific gene knockdown. The temporality and extent of siRNA-induced down-regulation were analyzed by targeting a transgene, EGFP, in mice overexpressing EGFP. Extensive knockdown of EGFP was observed, especially in regions adjacent or dorsoventrally and mediolaterally distant to the infusion site (dorsal third ventricle), with lesser knockdown in more distal regions. We challenged our RNAi approach to generate a specific knockdown of an endogenous gene, encoding the dopamine transporter (DAT) in regions (ventral midbrain) far distal to the infusion site. DAT-siRNA infusion in adult mice produced a significant down-regulation of DAT mRNA and protein in the brain and also elicited a temporal hyperlocomotor response similar to that (but delayed) obtained upon infusion of GBR-12909, a pharmacologically selective DAT inhibitor. Application of this nonviral RNAi approach may accelerate target validation for neuropsychiatric disorders that involve a complex interplay of gene(s) from various brain regions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.