Numerous mood and behavior disorders have developmental origins resulting from genetic and environmental interactions. Maternal Tryptophan Hydroxylase 1 (TPH-1)-dependent serotonin (5-HT) depletion alters embryonic brain development, but its long-term impact on adult progeny has never been investigated. Here we demonstrate that adult WT male offspring born to hyposerotonergic Tph1+/- dams (~60% reduction in maternal circulating 5-HT) display hyperlocomotion, impaired self-care and an increased anxiety relative to those from WT dams. Concomitantly, norepinephrine (NE) levels and dopamine (DA) turnover are significantly reduced in the mesencephalon and brainstem, whereas monoaminergic cell density is not affected. In the frontal cortex of the offspring, maternal hyposerotonergic status results in significant reduction in DA, NE and 5-HT levels, accompanied by transcriptomic changes, notably in monoaminergic system signaling, synaptic function and plasticity, methylation processes and myelination. Myelination is also impaired as revealed by a reduced thickness of the corpus callosum. Maternal hyposerotonemia thus appears sufficient to affect the phenotype of the adult WT progeny. TPH-1-dependent 5-HT deficit during pregnancy could be considered as a risk factor for neurodevelopmental disorders in the offspring.

Tania Vitalis is affiliated with Paris City University, France, where her research focuses on neuroscience and medicine, with particular expertise in cellular and molecular neuroscience, neurology, pediatrics, perinatology and child health, cognitive neuroscience, and behavioral neuroscience. Her research explores neuroinflammation and neurodegeneration, neonatal and fetal brain pathology, blood-brain barrier structure and function, memory and neural mechanisms, stress responses and cortisol, and neonatal brain and respiratory health. She has published extensively in international scientific journals, including Journal of Neural Transmission, Neuropathology and Applied Neurobiology, Current Issues in Molecular Biology, PLOS ONE, and médecine/sciences. Her recent research includes studies on the 5-HT7 receptor and perinatal white matter injury, blood-brain barrier permeability, neuroprotection following neonatal stroke, GABAergic neurons and neural mechanisms, and the neurobiology of traumatic stress.