Tyrosine Hydroxylase Expression in Differentiating Neurons of the Rat Arcuate Nucleus: Stimulatory Influence of Serotonin Afferents

The influence of serotonin afferents on tyrosine hydroxylase expression in differentiating neurons of the rat arcuate nucleus was studied in vivo and in vitro. In the in vivo study, pchlorophenylalanine inhibited serotonin synthesis in fetal brain from the 11th to the 20th embryonic day. We then used semiquantitative immunocytochemistry to evaluate tyrosine hydroxylase levels in neurons of the arcuate nucleus in fetuses at the 21st embryonic day or in offspring at the 35th postnatal day. Serotonin depletion significantly decreased the tyrosine hydroxylase content in neurons of males and females at the 21st embryonic day and in males at the 35th postnatal day. For the in vitro study, embryonic neurons of the arcuate nucleus were cocultured with embryonic neurons of the raphe nucleus, the main source of serotonin innervation of the brain, including the arcuate nucleus. Co-culture of the neurons resulted in a gender-specific increase of the tyrosine hydroxylase level in the neurons of the arcuate nucleus. In turn, the neurons of the raphe nucleus showed increased levels of serotonin in both males and females, with no sexual dimorphism. Thus, our results suggest a stimulatory, long-lasting effect of serotonin afferents on tyrosine hydroxylase expression in the differentiating neurons of the rat arcuate nucleus during prenatal ontogenesis.