ArticleACS chemical neuroscience2015
Pet-1 Controls Tetrahydrobiopterin Pathway and Slc22a3 Transporter Genes in Serotonin Neurons.
Article in ACS chemical neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Effects of SSRIs on the spatial transcriptome of dorsal raphe serotonin neurons.Molecular psychiatry · 2026Article
- Article
- Systematic analysis to identify transcriptome-wide dysregulation of Alzheimer's disease in genes and isoforms.Human genetics · 2021Article
- Tetrahydrobioterin (BH4) Pathway: From Metabolism to Neuropsychiatry.Current neuropharmacology · 2021Review
- Article
- Dopamine DThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Embracing diversity in the 5-HT neuronal system.Nature reviews. Neuroscience · 2019Review
- α1ACT Is Essential for Survival and Early Cerebellar Programming in a Critical Neonatal Window.Neuron · 2019Article
- Effects of chronic caffeine exposure during adolescence and subsequent acute caffeine challenge during adulthood on rat brain serotonergic systems.Neuropharmacology · 2019Article
- Ablation of Central Serotonergic Neurons Decreased REM Sleep and Attenuated Arousal Response.Frontiers in neuroscience · 2018Article
- Serotonin neuron development: shaping molecular and structural identities.Wiley interdisciplinary reviews. Developmental biology · 2018Review
- Serotonin transporter gene promoter methylation status correlates with in vivo prefrontal 5-HTT availability and reward function in human obesity.Translational psychiatry · 2017Article
- Pet-1 Switches Transcriptional Targets Postnatally to Regulate Maturation of Serotonin Neuron Excitability.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Coordinated serotonin (5-HT) synthesis and reuptake depends on coexpression of Tph2, Aadc (Ddc), and Sert (Slc6a4) in brain 5-HT neurons. However, other gene products play critical roles in brain 5-HT synthesis and transport. For example, 5-HT synthesis depends on coexpression of genes encoding the enzymatic machinery necessary for the production and regeneration of tetrahydrobiopterin (BH4). In addition, the organic cation transporter 3 (Oct3, Slc22a3) functions as a low affinity, high capacity 5-HT reuptake protein in 5-HT neurons. The regulatory strategies controlling BH4 and Oct3 gene expression in 5-HT neurons have not been investigated. Our previous studies showed that Pet-1 is a critical transcription factor in a regulatory program that controls coexpression of Tph2, Aadc, and Sert in 5-HT neurons. Here, we investigate whether a common regulatory program determines global 5-HT synthesis and reuptake through coordinate transcriptional control. We show with comparative microarray profiling of flow sorted YFP(+) Pet-1(-/-) and wild type 5-HT neurons that Pet-1 regulates BH4 pathway genes, Gch1, Gchfr, and Qdpr. Thus, Pet-1 coordinates expression of all rate-limiting enzymatic (Tph2, Gch1) and post-translational regulatory (Gchfr) steps that determine the level of mammalian brain 5-HT synthesis. Moreover, Pet-1 globally controls acquisition of 5-HT reuptake in dorsal raphe 5-HT neurons by coordinating expression of Slc6a4 and Slc22a3. In situ hybridizations revealed that virtually all 5-HT neurons in the dorsal raphe depend on Pet-1 for Slc22a3 expression; similar results were obtained for Htr1a. Therefore, few if any 5-HT neurons in the dorsal raphe are resistant to loss of Pet-1 for their full neuron-type identity.
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