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

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
PMID: 18663366
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Research groups Progéniteurs neuronaux (141)
Groupe Dayer Alexandre (Formation du circuit cortical) (875)
Anesthésie et neurosciences (883)
(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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