Altered Neocortical Cell Density and Layer Thickness in Serotonin Transporter Knockout Mice: A Quantitation Study
Open accessAbstract
The neurotransmitter serotonin (5-HT) plays morphogenetic roles during development, and their alteration could contribute to autism pathogenesis in humans. To further characterize 5-HT's contributions to neocortical development, we assessed the thickness and neuronal cell density of various cerebral cortical areas in serotonin transporter (5-HTT) knockout (ko) mice, characterized by elevated extracellular 5-HT levels. The thickness of layer IV is decreased in 5-HTT ko mice compared with wild-type (wt) mice. The overall effect on cortical thickness, however, depends on the genetic background of the mice. Overall cortical thickness is decreased in many cortical areas of 5-HTT ko mice with a mixed c129-CD1-C57BL/6J background. Instead, 5-HTT ko mice backcrossed into the C57BL/6J background display increases in supragranular and infragranular layers, which compensate entirely for decreased layer IV thickness, resulting in unchanged or even enhanced cortical thickness. Moreover, significant increases in neuronal cell density are found in 5-HTT ko mice with a C57BL/6J background (wt:hz:ko ratio = 1.00:1.04:1.17) but not in the mixed c129-CD1-C57BL/6J 5-HTT ko animals. These results provide evidence of 5-HTT gene effects on neocortical morphology in epistatic interaction with genetic variants at other loci and may model the effect of functional 5-HTT gene variants on neocortical development in autism.
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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.
“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 [238]
The Abstract (page unavailable) describes serotonin receptors on neural progenitor cells during embryonic development. The Discussion (page unavailable) says thalamocortical endings transiently express the transporter and a receptor during early postnatal life in rodents. Neither passage establishes expression at rodent E10 or human weeks 4–5, expression of synthesizing enzymes, or expression before axonal projections reach the PFC. (LLM, conf=0.82)
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- Authors
- Altamura, C., Dell'Acqua, M., Moessner, R., Murphy, D., Lesch, K., & Persico, A. M.
- Affiliations
- Università Campus Bio-Medico (IT)
- University of Würzburg (DE)
- National Institutes of Health (US)
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-08-11
- Volume
- 17
- Issue
- 6
- Pages
- 1394-1401
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2118607105
- Cited by
- 79
- References
- 63
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 6 · 2017: 4 · 2016: 5 · 2015: 5 · 2014: 4 · 2013: 8 · 2012: 8
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- serotonin transporter, 5-HTT knockout mice, neocortex development, cortical thickness, neuronal density, cortical layers, layer 4, genetic background, epistasis, autism spectrum disorder, serotonin
- MeSH terms
- Animals, Autistic Disorder, Cell Count, Cell Division, Disease Models, Animal, Epistasis, Genetic, Extracellular Space, Female, Male, Mice, Inbred C57BL, Neurons, Serotonin, Apoptosis, Mice, Knockout, Neocortex, Serotonin Plasma Membrane Transport Proteins, Mice
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