ArticleMolecular psychiatry2005
siRNA-mediated knockdown of the serotonin transporter in the adult mouse brain.
Article in Molecular psychiatry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 157 citations in OpenAlex.
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- Depressive disorders: Treatment failures and poor prognosis over the last 50 years.Pharmacology research & perspectives · 2019Review
- The Gain-of-Function Integrin β3 Pro33 Variant Alters the Serotonin System in the Mouse Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- The therapeutic and diagnostic potential of the prostate specific membrane antigen/glutamate carboxypeptidase II (PSMA/GCPII) in cancer and neurological disease.British journal of pharmacology · 2016Review
- Adropin acts in brain to inhibit water drinking: potential interaction with the orphan G protein-coupled receptor, GPR19.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Article
- Therapeutic antidepressant potential of a conjugated siRNA silencing the serotonin transporter after intranasal administration.Molecular psychiatry · 2016Article
- Article
- Nanoparticles and the blood-brain barrier: advancing from in-vitro models towards therapeutic significance.Pharmaceutical research · 2015Review
- 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
- RNAi-mediated serotonin transporter suppression rapidly increases serotonergic neurotransmission and hippocampal neurogenesis.Translational psychiatry · 2013Article
- Acute 5-HT₁A autoreceptor knockdown increases antidepressant responses and serotonin release in stressful conditions.Psychopharmacology · 2013Article
- MicroRNA as therapeutic targets for treatment of depression.Neuropsychiatric disease and treatment · 2013Article
- Evidence for an interaction of neuronostatin with the orphan G protein-coupled receptor, GPR107.American journal of physiology. Regulatory, integrative and comparative physiology · 2012Article
- Click-modified cyclodextrins as nonviral vectors for neuronal siRNA delivery.ACS chemical neuroscience · 2012Article
- Illuminating the gateway of gene silencing: perspective of RNA interference technology in clinical therapeutics.Molecular biotechnology · 2012Review
- Targeting the BH3-interacting domain death agonist to develop mechanistically unique antidepressants.Molecular psychiatry · 2012Article
- Selective siRNA-mediated suppression of 5-HT1A autoreceptors evokes strong anti-depressant-like effects.Molecular psychiatry · 2012Article
- Activation of the Nrf2-ARE pathway by siRNA knockdown of Keap1 reduces oxidative stress and provides partial protection from MPTP-mediated neurotoxicity.Neurotoxicology · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressant drugs that increase the extracellular levels of serotonin by blocking the reuptake activity of the serotonin transporter (SERT). Although SSRIs elevate brain serotonergic neurotransmission acutely, their full therapeutic effects involve neurochemical adaptations that emerge following chronic drug administration. The adaptive downregulation of SERT has recently been implicated in the therapeutic response of SSRIs. Interestingly, studies using SERT-knockout mice reveal somewhat paradoxical depression-related effects, probably specific to the downregulation of SERT during early development. However, the behavioral significance of SSRI-mediated downregulation of SERT during adulthood is still unknown. We investigated whether somatic gene manipulation, triggered by infusing short interfering RNA (siRNA) into the ventricular system, would enable the downregulation of SERT in the adult mouse brain. Infusing the SERT-targeting siRNA, for 2 weeks, significantly reduced the mRNA levels of SERT in raphe nuclei. Further, a significant, specific and widespread downregulation of SERT-binding sites was achieved in the brain. In contrast, 2-week infusion of the SSRI, citalopram, produced a widespread downregulation of SERT-binding sites, independent of any alterations at the mRNA level. Irrespective of their mechanisms for downregulating SERT in the brain, infusions of SERT-siRNA or citalopram elicited a similar antidepressant-related behavioral response in the forced swim test. These results signify a role for the downregulation of SERT in mediating the antidepressant action of SSRIs in adults. Further, these data demonstrate that siRNA-induced widespread knockdown of gene expression serves as a powerful tool for assessing the function of endogenous genes in the adult brain.
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Registered trials
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.