ArticleMolecular psychiatry2012
Selective siRNA-mediated suppression of 5-HT1A autoreceptors evokes strong anti-depressant-like effects.
Article in Molecular psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 117 citations in OpenAlex.
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- The therapeutic potential of psilocybin beyond psychedelia through shared mechanisms with ketamine.Molecular psychiatry · 2025Review
- A New Augmentation Strategy against Depression Combining SSRIs and the N-terminal Fragment of Galanin (1-15).Current neuropharmacology · 2025Review
- CaMKIV-Mediated Phosphorylation Inactivates Freud-1/CC2D1A Repression for Calcium-Dependent 5-HT1A Receptor Gene Induction.International journal of molecular sciences · 2024Article
- Dual HDAC/BRD4 Inhibitors Relieves Neuropathic Pain by Attenuating Inflammatory Response in Microglia After Spared Nerve Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- The Implication of 5-HT Receptor Family Members in Aggression, Depression and Suicide: Similarity and Difference.International journal of molecular sciences · 2022Review
- 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
- mTOR Knockdown in the Infralimbic Cortex Evokes A Depressive-like State in Mouse.International journal of molecular sciences · 2021Article
- 5-HTACS chemical neuroscience · 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
- Targeting Beclin1 as an Adjunctive Therapy against HIV Using Mannosylated Polyethylenimine Nanoparticles.Pharmaceutics · 2021Article
- Effects of Subchronic Administrations of Vortioxetine, Lurasidone, and Escitalopram on Thalamocortical Glutamatergic Transmission Associated with Serotonin 5-HT7 Receptor.International journal of molecular sciences · 2021Article
- 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
- Antidepressant-Like Effects of CX717, a Positive Allosteric Modulator of AMPA Receptors.Molecular neurobiology · 2020Article
- β-Catenin Role in the Vulnerability/Resilience to Stress-Related Disorders Is Associated to Changes in the Serotonergic System.Molecular neurobiology · 2020Article
- Modulation of Monoaminergic Systems by Antidepressants in the Frontal Cortex of Rats After Chronic Mild Stress Exposure.Molecular neurobiology · 2019Article
- Functional Interrogation of a Depression-Related Serotonergic Single Nucleotide Polymorphism, rs6295, Using a Humanized Mouse Model.ACS chemical neuroscience · 2019Article
- Serotonergic system, cognition, and BPSD in Alzheimer's disease.Neuroscience letters · 2019Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Depression is a major health problem worldwide. Most prescribed anti-depressants, the selective serotonin reuptake inhibitors (SSRI) show limited efficacy and delayed onset of action, partly due to the activation of somatodendritic 5-HT(1A)-autoreceptors by the excess extracellular serotonin (5-HT) produced by SSRI in the raphe nuclei. Likewise, 5-HT(1A) receptor (5-HT(1A)R) gene polymorphisms leading to high 5-HT(1A)-autoreceptor expression increase depression susceptibility and decrease treatment response. In this study, we report on a new treatment strategy based on the administration of small-interfering RNA (siRNA) to acutely suppress 5-HT(1A)-autoreceptor-mediated negative feedback mechanisms. We developed a conjugated siRNA (C-1A-siRNA) by covalently binding siRNA targeting 5-HT(1A) receptor mRNA with the SSRI sertraline in order to concentrate it in serotonin axons, rich in serotonin transporter (SERT) sites. The intracerebroventricular (i.c.v.) infusion of C-1A-siRNA to mice resulted in its selective accumulation in serotonin neurons. This evoked marked anti-depressant-like effects in the forced swim and tail suspension tests, but did not affect anxiety-like behaviors in the elevated plus-maze. In parallel, C-1A-siRNA administration markedly decreased 5-HT(1A)-autoreceptor expression and suppressed 8-OH-DPAT-induced hypothermia (a pre-synaptic 5-HT(1A)R effect in mice) without affecting post-synaptic 5-HT(1A)R expression in hippocampus and prefrontal cortex. Moreover, i.c.v. C-1A-siRNA infusion augmented the increase in extracellular serotonin evoked by fluoxetine in prefrontal cortex to the level seen in 5-HT(1A)R knockout mice. Interestingly, intranasal C-1A-siRNA administration produced the same effects, thus opening the way to the therapeutic use of C-1A-siRNA. Hence, C-1A-siRNA represents a new approach to treat mood disorders as monotherapy or in combination with SSRI.
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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.