Impact of maternal blood hyposerotonemia on adult wild-type progeny
Numerous mood and behavior disorders have developmental origin resulting from genetic and environmental interactions. Maternal blood serotonin (5-HT) depletion alters embryonic brain development, but its long-term impact on progeny has never been investigated. Here we demonstrate that maternal blood hyposerotonemia (60% deficit) induced hyperlocomotion, self-care deficit and increased anxiety in adult WT male offspring. Concomitantly, norepinephrine (NE) level and dopamine (DA) turnover were significantly reduced in the mesencephalon and brainstem, whereas monoaminergic cell density was not affected. In the frontal cortex, maternal hyposerotonemia caused a 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 was also defective as revealed by a reduced thickness of the corpus callosum. Maternal hyposerotonemia is thus sufficient to affect the phenotype of adult WT progeny. Maternal peripheral 5-HT deficit during pregnancy could thus be considered as a risk factor for neurodevelopmental disorders in the offspring.
Numerous mood and behavior disorders have developmental origin resulting from genetic and environmental interactions. Maternal blood serotonin (5-HT) depletion alters embryonic brain development, but its long-term impact on progeny has never been investigated. Here we demonstrate that maternal blood hyposerotonemia (60% deficit) induced hyperlocomotion, self-care deficit and increased anxiety in adult WT male offspring. Concomitantly, norepinephrine (NE) level and dopamine (DA) turnover were significantly reduced in the mesencephalon and brainstem, whereas monoaminergic cell density was not affected. In the frontal cortex, maternal hyposerotonemia caused a 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 was also defective as revealed by a reduced thickness of the corpus callosum. Maternal hyposerotonemia is thus sufficient to affect the phenotype of adult WT progeny. Maternal peripheral 5-HT deficit during pregnancy could thus be considered as a risk factor for neurodevelopmental disorders in the offspring.
European Bioinformatics Institute