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Study reveals placentaís role in producing serotonin

BY: BILL SNYDER

4/21/2011 - The placenta not only transfers oxygen and nutrients from mother to fetus, it also produces the potent brain chemical serotonin during a critical stage in fetal development.

The finding by researchers at the University of Southern California (USC), Vanderbilt University and Case Western Reserve University overturns 60 years of conventional wisdom, which held that serotonin was supplied by the mother's blood supply.

Their study, which appears in the current issue of the journal Nature, suggests that one day it may be possible to intervene in high-risk pregnancies where a “perturbed” intrauterine environment might negatively impact fetal brain development.

“The placenta was seen as a passive organ, but we now know that it has significant synthetic capabilities and has a much more critical role in developmental programming of the fetus than previously thought,” said Alexandre Bonnin, Ph.D., lead author of the study and assistant professor of research at USC's Zilkha Neurogenetic Institute.

“This is an important finding that suggests that the maternal/fetal environment, acting through serotonin, plays a big role in how the brain develops that can have significant medical consequences after birth,” added co-author Randy Blakely, Ph.D., program director of the Vanderbilt Silvio O. Conte Center for Neuroscience Research.

Randy Blakely, Ph.D.

Randy Blakely, Ph.D.

Evan Deneris, Ph.D., professor of Neurosciences at Case Western Reserve University, collaborated in the study, conducted as part of a Conte Center of Excellence grant from the National Institute of Mental Health.

Bonnin's work with Pat Levitt, Ph.D., director of the Zilkha Neurogenetic Institute and corresponding author on the paper, included the invention of a unique technology called a “placentometer” that monitors substances passing through the mouse placenta from mother to fetus. The researchers also showed the human placenta has the same capacity to produce serotonin.

Serotonin, which plays an important role in mood, sleep and cognition, also has been implicated in development of the pancreas, heart and brain. Disruptions in “fetal programming” may contribute to adult-onset disorders such as diabetes, heart disease and mental illness.

In the early stages of development, neurons that synthesize serotonin develop in the fetal hindbrain, where heart, respiration and other critical functions reside, eventually building their way up to the forebrain, the home of higher cognition and emotional regulation.

The study shows that during this gap between hindbrain and forebrain serotonin development, the placenta is an important source of serotonin to the forebrain — a process that could be affected by the mother's nutrition, since her diet is the only source for the essential amino acid tryptophan.

This may be particularly relevant to early-onset disorders such as autism, Asperger's syndrome and pediatric obsessive-compulsive disorder, where human genetic studies have implicated a possible role for serotonin, Blakely said.

Levitt, chair of Cell and Neurobiology at the Keck School of Medicine of USC, is former director of the Vanderbilt Kennedy Center for Research on Human Development.

Bonnin, a former Vanderbilt postdoctoral research fellow in Pharmacology, is supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by a NARSAD Young Investigator Award.

— Leslie Ridgeway contributed to this story

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