Neuroscience Forefront ReviewFetal, maternal, and placental sources of serotonin and new implications for developmental programming of the brain
Highlights
▶Serotonin signaling affects fetal brain development. ▶During an early phase of pregnancy, the placenta provides serotonin to the fetal brain. ▶Placenta-derived serotonin may be important for normal fetal brain development. ▶Results suggest new maternal–fetal–placental contributions to the fetal programming of adult mental disorders.
Section snippets
Role of 5-HT in fetal forebrain wiring
Anatomical studies have shown the early appearance of serotonergic neurons in the developing hindbrain and suggested a role for 5-HT in fetal brain development (Lidov and Molliver, 1982, Aitken and Törk, 1988, Buznikov et al., 2001). These neurons differentiate in the fetal dorsal raphe (DR) as early as embryonic day (E) 10.5 in the mouse and send axons through the ventral forebrain via the medial forebrain bundle; by E14.5 some 5-HT axons are already reaching rostral regions, including the
Sources of 5-HT in the fetal forebrain
Over the past 40 years, the field has embraced the concept that there are both fetal and maternal contributions of 5-HT during pregnancy. Serotonergic neurons appear early in the fetal hindbrain and could provide an endogenous source of 5-HT. Sources of 5-HT other than the fetal brain was assumed because of the observations that 5-HT receptors expression in the rostral forebrain, craniofacial, and peripheral regions is evident several days before serotonergic axons even reach these regions (
Conclusion
The results summarized here provide a mechanism through which alterations of tryptophan metabolic pathways in the placenta can affect placental 5-HT synthesis and fetal forebrain development. We showed that there is a progressive switch from an early dependence on an exogenous (placental) source of 5-HT to a later endogenous brain source. The placental source of 5-HT is provided to the forebrain during developmental periods that include cortical neurogenesis, migration, and initial axon
Acknowledgments
We thank Nick Goeden for technical help. This work was supported by the NICHD (grant 5R21HD065287 to A.B.), NARSAD (to A.B.) and the NIMH (grant 1P50MH078280A1 to P.L.).
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