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Title

Excess of serotonin affects embryonic interneuron migration through activation of the serotonin receptor 6

Authors
Riccio, Orbicia
Szabó, G.
Published in Molecular Psychiatry. 2009, vol. 14, no. 3, p. 280-90
Abstract The discovery that a common polymorphism (5-HTTLPR, short variant) in the human serotonin transporter gene (SLC6A4) can influence personality traits and increase the risk for depression in adulthood has led to the hypothesis that a relative increase in the extracellular levels of serotonin (5-HT) during development could be critical for the establishment of brain circuits. Consistent with this idea, a large body of data demonstrate that 5-HT is a strong neurodevelopmental signal that can modulate a wide variety of cellular processes. In humans, serotonergic fibers appear in the developing cortex as early as the 10th gestational week, a period of intense neuronal migration. In this study we hypothesized that an excess of 5-HT could affect embryonic cortical interneuron migration. Using time-lapse videometry to monitor the migration of interneurons in embryonic mouse cortical slices, we discovered that the application of 5-HT decreased interneuron migration in a reversible and dose-dependent manner. We next found that 5-HT6 receptors were expressed in cortical interneurons and that 5-HT6 receptor activation decreased interneuron migration, whereas 5-HT6 receptor blockade prevented the migratory effects induced by 5-HT. Finally, we observed that interneurons were abnormally distributed in the cerebral cortex of serotonin transporter gene (Slc6a4) knockout mice that have high levels of extracellular 5-HT. These results shed new light on the neurodevelopmental alterations caused by an excess of 5-HT during the embryonic period and contribute to a better understanding of the cellular processes that could be modulated by genetically controlled differences in human 5-HT homeostasis.
Keywords AnimalsCell Movement/drug effects/physiologyCerebral Cortex/cytology/embryology/physiologyCritical Period (Psychology)Dose-Response Relationship, DrugInterneurons/cytology/metabolismMiceMice, Inbred C57BLMice, KnockoutOrgan Culture TechniquesReceptors, Serotonin/metabolismSerotonin/administration & dosage/physiologySerotonin Plasma Membrane Transport Proteins/genetics/metabolism
Identifiers
PMID: 18663366
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Structures
Research groups Progéniteurs neuronaux (141)
Groupe Dayer Alexandre (Formation du circuit cortical) (875)
Anesthésie et neurosciences (883)
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(ISO format)
RICCIO, Orbicia et al. Excess of serotonin affects embryonic interneuron migration through activation of the serotonin receptor 6. In: Molecular psychiatry, 2009, vol. 14, n° 3, p. 280-90. https://archive-ouverte.unige.ch/unige:3855

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Deposited on : 2009-10-22

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