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Serotonin transporter transgenic (SERTcre) mouse line reveals developmental targets of serotonin specific reuptake inhibitors (SSRIs)
Open accessAbstract
The serotonin transporter gene (SLC6A4; synonyms, SERT, 5-HTT) is expressed much more broadly during development than in adulthood. To obtain a full picture of all sites of SERT expression during development we used a new mouse model where Cre recombinase was inserted into the gene encoding the serotonin transporter. Two reporter mouse lines, ROSA26R and the Tau(mGFP), allowed to map all the cells that express SERT at any point during development. Combined LacZ histochemistry and GFP immunolabelling showed neuronal cell bodies and axon fiber tracts. Earliest recombination in embryos was visible in the periphery in the heart and liver by E10.5 followed by recombination in the brain in raphe serotonergic neurons by E12.5. Further, recombination in non-serotonin neurons was visible in the choroid plexus, roof plate, and neural crest derivatives; by E15.5, recombination was found in the dorsal thalamus, cingulate cortex, CA3 field of the hippocampus, retinal ganglion cells, superior olivary nucleus and cochlear nucleus. Postnatally, SERT mediated recombination was visible in the medial prefrontal cortex and layer VI neurons in the isocortex. Recombined cells were co-labelled with Neu-N, but not with GAD67, and were characterized by long range projections (corpus callosum, fornix, thalamocortical). This fate map of serotonin transporter expressing cells emphasizes the broad expression of SERT in non-serotonin neurons during development and clarifies the localization of SERT expression in the hippocampus and limbic cortex. The identification of targets of SSRIs and serotonin releasers during embryonic and early postnatal life helps understanding the very diverse physiological consequences of administration of these drugs during development.
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“Receptors, transporters as well as synthesizing enzymes are already expressed (~E10 rodent and week 4–5 human) even when the actual axonal projections have not yet arrived in the PFC [236–240].”
From Development of prefrontal cortex (2022) · cites this paper as [237]
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Self-citation
Metadata
- Authors
- Narboux-Nême, N., Pavone, L. M., Avallone, L., Zhuang, X., & Gaspar, P.
- Affiliations
- University of Naples Federico II (IT)
- University of Chicago (US)
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 55
- Issue
- 6
- Pages
- 994-1005
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2013740680
- Cited by
- 148
- References
- 72
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 13 · 2020: 16 · 2019: 11 · 2018: 9 · 2017: 14 · 2016: 10 · 2015: 6 · 2014: 11 · 2013: 6 · 2012: 6
- FWCI
- 3.46
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Funders
- European Commission (201714)
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- serotonin transporter, selective serotonin reuptake inhibitors, developmental gene expression, Cre recombinase, fate mapping, embryonic development, choroid plexus, neural crest derivatives, hippocampus, limbic cortex, medial prefrontal cortex, axonal projections
- MeSH terms
- Animals, Embryo, Mammalian, Mice, Transgenic, Neurons, Raphe Nuclei, Serotonin, tau Proteins, Selective Serotonin Reuptake Inhibitors, Gene Expression Regulation, Developmental, Integrases, Green Fluorescent Proteins, Serotonin Plasma Membrane Transport Proteins, Mice
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