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

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  • 2008-07-30
Published in:
  • Molecular psychiatry. - 2009
Animals
Cell Movement
Cerebral Cortex
Critical Period, Psychological
Dose-Response Relationship, Drug
Interneurons
Mice
Mice, Inbred C57BL
Mice, Knockout
Organ Culture Techniques
Receptors, Serotonin
Serotonin
Serotonin Plasma Membrane Transport Proteins
English 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.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/240153
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