Serotonin may act as a growth factor for the stem cells...

During human evolution, the size of the brain increased, particularly in a specific part called the neocortex. The neocortex enables us to speak, dream and think. In search of the causes of the neocortex expansion, researchers at the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden, together with colleagues from the Carl Gustav Carus University Hospital in Dresden, identified a number of molecular actors. These actors typically work in the so-called basal precursors, the stem cells in the developing neocortex, which play a central role in its expansion. The researchers now report an additional, novel role of the happiness neurotransmitter serotonin, which is known to mediate satisfaction, self-confidence and optimism in the brain – cell-extrinsically as a growth factor for basic precursors in developing humans. but not mouse, neocortex. Because of this new function, placenta-derived serotonin likely contributed to the evolutionary expansion of the human neocortex.

Wieland Huttner’s research team at the Max Planck Institute for Molecular Cell Biology and Genetics, one of the institute’s founding directors, has conducted many studies to investigate the cause of the evolutionary expansion of the human neocortex. A new study from his laboratory looks at the role of the neurotransmitter serotonin in this process. Serotonin is often referred to as a happiness neurotransmitter because it carries messages between nerve cells that contribute to well-being and happiness. However, a possible role for such neurotransmitters during brain development has not yet been studied in detail. In the developing embryo, the placenta produces serotonin, which then enters the brain via the bloodstream. This applies to both humans and mice. However, the function of this placenta-derived serotonin in the developing brain is unknown.

Postdoc Lei Xing from the Huttner group studied neurotransmitters while doing his doctorate in Canada. When he then started his research project in Dresden, he was curious to investigate their role in the developing brain. Lei Xing says, “I took advantage of data sets generated by the group in the past and found that the serotonin receptor HTR2A was expressed in the fetal human but not the mouse embryonic neocortex. Serotonin has to bind to this receptor in order to activate the downstream signal transmission. I. wondered if this receptor could be one of the keys to why people have bigger brains. “To study this, the researchers induced the production of the HTR2A receptor in the mouse embryonic neocortex. “In fact, we found that by activating this receptor, serotonin set off a chain of reactions that resulted in the production of more basal precursors in the developing brain. More basal precursors can then increase the production of cortical neurons, paving the way for a bigger brain, “continues Lei Xing.

Significance for the development and evolution of the brain

“In summary, our study shows a novel role for serotonin as a growth factor for basal precursors in highly developed brains, especially in humans. Our data implies serotonin in the expansion of the neocortex during development and human evolution, ”summarizes Wieland Huttner, who carried out the monitoring of the study. He continues: “Abnormal signals of serotonin and impaired expression or mutation of its HTR2A receptor have been observed in various neurodevelopmental and psychiatric disorders such as Down’s syndrome, attention deficit hyperactivity disorder and autism. Our results could explain how malfunctioning of serotonin and its receptor during development of the fetal brain can lead to congenital disorders and suggest new approaches for therapeutic avenues. ”

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