The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Expression of serotonin transporter protein in developing rat brain
Abstract
Serotonin transporter (5-HTT), a transmembrane protein, has been shown in adult brain to be distributed not only on synaptic terminals but to a great extent on axons as well. Here we report the ontogeny of 5-HTT and its relationship with serotonin (5-HT) neurons using established 5-HTT and 5-HT antibodies. Both 5-HTT- and 5-HT-immunostaining (-im) appear in 5-HT neurons at embryonic day 12 (E12) in rostral raphe nuclei (RRN). Soon after appearing, 5-HTT-im is highly expressed on axons, similar to adult expression. However, in contrast to adult, 5-HTT-im also outlines the soma-dendrites. Rich 5-HTT-im appears along the entire length of projecting axons, extending to the growth tip. In the next 2 days, intensive 5-HTT-im axons from RRN travel a course preferentially in the floor plate and later, the medial forebrain bundle trajectory. A group of new 5-HT-im neurons and 5-HTT-im axons appear at E13 in caudal raphe nuclei. At E16-18, taking the exact trajectory course of 5-HT axons, 5-HTT-im axons reach ganglionic eminence, olfactory bulb, and cortex and disperse into many brain regions in E18-20. No 5-HTT-im cell bodies were seen in nigral, locus ceruleus, or hypothalamus. However, the transient expression of 5-HTT on non-serotonergic system was seen in cortical and striatal neuroepithelia at E12 and sensory thalamic pathways at P0-P10. Prominent 5-HTT-im fibers in thalamocortical bundles project from sensory thalamic nuclei through reticular nucleus, internal capsule bundle and form barrels in somatosensory cortices. No 5-HTT-im was seen in glia-like cells using currently available antibody. These observations indicate that 5-HTT is: (a) associated preferentially with 5-HT neurons in brainstem, (b) temporally co-expressed with 5-HT in 5-HT neurons, (c) expressed on axons prior to synaptical sites at target neurons, which strongly indicates a volumic (extrasynaptic) transmission, (d) expressed in non-5-HT neurons within a specific window, which may affect the development of the systems "borrowing" the 5-HT. The early appearance of 5-HTT may also endow functionality as well as vulnerabilities of 5-HT, sensory thalamic, and cortical neurons to 5-HTT targeting drugs during pregnancy and after birth.
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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 [236]
Citations
Cites
Cloning and expression of a functional serotonin transporter from rat brain
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Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors
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Development of prefrontal cortex
Kolk, S. M., & Rakic, P. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-021-01137-9 · Cited by 378
Brenhouse, H. C., & Andersen, S. L. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.04.013 · Cited by 363
Neonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry
Maciąg, D., Simpson, K. L., Coppinger, D., Lu, Y., Wang, Y., Lin, R. C. S., & Paul, I. A. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300823 · Cited by 309
Metadata
- Authors
- Zhou, F. C., Sari, Y., & Zhang, J. K.
- Affiliations
- Indiana University School of Medicine (US)
- Corresponding author
- Zhou, Feng C
- Venue
- Developmental Brain Research
- Publisher
- Elsevier BV
- Published
- 2000-01
- Volume
- 119
- Issue
- 1
- Pages
- 33-45
- ISSN
- 0165-3806 (ISSN-L)
- OpenAlex
- W1965084584
- Cited by
- 111
- References
- 47
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 8 · 2015: 5 · 2014: 1 · 2013: 7 · 2012: 2
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Developmental Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r03mh050602-02)
- National Institute on Alcohol Abuse and Alcoholism (P50AA07611-11, P50AA007611)
- National Institute of Mental Health (R03MH50602)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- serotonin transporter, serotonergic neurons, ontogeny, axon trajectory, floor plate, medial forebrain bundle, ganglionic eminence, olfactory bulb, thalamocortical circuits, sensory thalamus
- MeSH terms
- Animals, Axons, Brain, Brain Mapping, Carrier Proteins, Cerebral Cortex, Dendrites, Gestational Age, Immunohistochemistry, Membrane Glycoproteins, Nerve Fibers, Nerve Tissue Proteins, Neuroglia, Neurons, Organ Specificity, Raphe Nuclei, RNA, Messenger, Serotonin, Thalamus, Rats, Sprague-Dawley, Membrane Transport Proteins, Serotonin Plasma Membrane Transport Proteins, Rats
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