ArticleMolecular psychiatry2016
Therapeutic antidepressant potential of a conjugated siRNA silencing the serotonin transporter after intranasal administration.
Article in Molecular psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 62 citations in OpenAlex.
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- Antidepressant-like Effects ofPharmaceuticals (Basel, Switzerland) · 2024Article
- ER stress in mouse serotonin neurons triggers a depressive phenotype alleviated by ketamine targeting eIF2α signaling.iScience · 2024Article
- Microbial bionic nano-aromatic drugs for prevention of depression induced by chronic stress.Journal of nanobiotechnology · 2024Article
- Dysfunctional serotonergic neuron-astrocyte signaling in depressive-like states.Molecular psychiatry · 2023Article
- Nucleic acid drug vectors for diagnosis and treatment of brain diseases.Signal transduction and targeted therapy · 2023Review
- Intracerebral administration of a modified antisense oligonucleotide targeting the dopamine system in a mouse model of Parkinson's disease.STAR protocols · 2022Article
- Chimeric Structures in Mental Illnesses-"Magic" Molecules Specified for Complex Disorders.International journal of molecular sciences · 2022Review
- Human α-synuclein overexpression in mouse serotonin neurons triggers a depressive-like phenotype. Rescue by oligonucleotide therapy.Translational psychiatry · 2022Article
- Up and Down γ-Synuclein Transcription in Dopamine Neurons Translates into Changes in Dopamine Neurotransmission and Behavioral Performance in Mice.International journal of molecular sciences · 2022Article
- Lipid nanoparticles for antisense oligonucleotide gene interference into brain border-associated macrophages.Frontiers in molecular biosciences · 2022Article
- mTOR Knockdown in the Infralimbic Cortex Evokes A Depressive-like State in Mouse.International journal of molecular sciences · 2021Article
- Intracerebral Administration of a Ligand-ASO Conjugate Selectively Reduces α-Synuclein Accumulation in Monoamine Neurons of Double Mutant Human A30P*A53T*α-Synuclein Transgenic Mice.International journal of molecular sciences · 2021Article
- Progress in the molecular pathogenesis and nucleic acid therapeutics for Parkinson's disease in the precision medicine era.Medicinal research reviews · 2020Review
- Anti-α-synuclein ASO delivered to monoamine neurons prevents α-synuclein accumulation in a Parkinson's disease-like mouse model and in monkeys.EBioMedicine · 2020Article
- β-Catenin Role in the Vulnerability/Resilience to Stress-Related Disorders Is Associated to Changes in the Serotonergic System.Molecular neurobiology · 2020Article
- Non-Coding RNAs in Psychiatric Disorders and Suicidal Behavior.Frontiers in psychiatry · 2020Review
- Genetic, epigenetic and posttranscriptional mechanisms for treatment of major depression: the 5-HT1A receptor gene as a paradigmJournal of psychiatry & neuroscience : JPN · 2019Review
- Selective Knockdown of TASK3 Potassium Channel in Monoamine Neurons: a New Therapeutic Approach for Depression.Molecular neurobiology · 2019Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Major depression brings about a heavy socio-economic burden worldwide due to its high prevalence and the low efficacy of antidepressant drugs, mostly inhibiting the serotonin transporter (SERT). As a result, ~80% of patients show recurrent or chronic depression, resulting in a poor quality of life and increased suicide risk. RNA interference (RNAi) strategies have been preliminarily used to evoke antidepressant-like responses in experimental animals. However, the main limitation for the medical use of RNAi is the extreme difficulty to deliver oligonucleotides to selected neurons/systems in the mammalian brain. Here we show that the intranasal administration of a sertraline-conjugated small interfering RNA (C-SERT-siRNA) silenced SERT expression/function and evoked fast antidepressant-like responses in mice. After crossing the permeable olfactory epithelium, the sertraline-conjugated-siRNA was internalized and transported to serotonin cell bodies by deep Rab-7-associated endomembrane vesicles. Seven-day C-SERT-siRNA evoked similar or more marked responses than 28-day fluoxetine treatment. Hence, C-SERT-siRNA (i) downregulated 5-HT1A-autoreceptors and facilitated forebrain serotonin neurotransmission, (ii) accelerated the proliferation of neuronal precursors and (iii) increased hippocampal complexity and plasticity. Further, short-term C-SERT-siRNA reversed depressive-like behaviors in corticosterone-treated mice. The present results show the feasibility of evoking antidepressant-like responses by selectively targeting neuronal populations with appropriate siRNA strategies, opening a way for further translational studies.
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