ArticleGene therapy2009
Targeting central serotonergic neurons with lentiviral vectors based on a transcriptional amplification strategy.
Article in Gene therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 32 citations in OpenAlex.
- A serotonergic axon-cilium synapse drives nuclear signaling to alter chromatin accessibility.Cell · 2022Article
- The Role of Dorsal Raphe Serotonin Neurons in the Balance between Reward and Aversion.International journal of molecular sciences · 2020Article
- Manipulation of dorsal raphe serotonergic neurons modulates active coping to inescapable stress and anxiety-related behaviors in mice and rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
- α-Synuclein induced toxicity in brain stem serotonin neurons mediated by an AAV vector driven by the tryptophan hydroxylase promoter.Scientific reports · 2016Article
- Lentiviral vectors as tools to understand central nervous system biology in mammalian model organisms.Frontiers in molecular neuroscience · 2015Review
- Comparative analysis of optogenetic actuators in cultured astrocytes.Cell calcium · 2014Article
- Cardioprotection evoked by remote ischaemic preconditioning is critically dependent on the activity of vagal pre-ganglionic neurones.Cardiovascular research · 2012Article
- Serotonin: a regulator of neuronal morphology and circuitry.Trends in neurosciences · 2010Review
- Gene transfer in the nervous system and implications for transsynaptic neuronal tracing.Expert opinion on biological therapy · 2010Review
- The use of viral gene transfer in studies of brainstem noradrenergic and serotonergic neurons.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2009Review
- Adenoviral vectors for highly selective gene expression in central serotonergic neurons reveal quantal characteristics of serotonin release in the rat brain.BMC biotechnology · 2009Article
- Selective optogenetic stimulation of efferent fibers in the vagus nerve of a large mammal.Brain stimulationArticle
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Numerous pathological processes have been linked to disorders of the central 5-hydroxytryptamine (5HT) system but the possibility of gene therapy through modulation of 5HT system remained unexplored due to the lack of the specific targeting vectors. We explored the sequences upstream of the tryptophan hydroxylase-2 (TPH-2) gene, the key enzyme in neuronal 5HT synthesis and generated lentiviral vectors, which were then tested in vivo using microinjections into the rat raphe. All fragments longer than 1 kb (called 2TPH, 3.6TPH and 6.7TPH) drove highly specific expression in 5HT neurons which was, however too weak to be detectable without immunostaining. To enhance the level of expression, a two-step transcriptional amplification strategy was employed whereby the activity of a TPH-2 promoter fragment was potentiated by a chimeric enhancer GAL4/p65. Surprisingly, previously published implementations of this strategy compromised the specificity of expression. We therefore used a new approach where both, the transgene and GAL4/p65 are co-expressed using an internal ribosomal entry site and GAL4/p65 operates in a positive feedback manner to amplify the expression. Thus, we have generated new vectors, which are both, highly specific for 5HT neurons and sufficiently powerful. They open a range of new opportunities for enquiries into genetic correction of 5HT-related disorders.
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Registered trials
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