Serotonin (5-HT, 5-hydroxytryptamine) is known to be an inductor of the brain development [Whitaker-Azmitia, P.M., Druse, M., Walker, P., Lauder, J.M., 1996. Serotonin as a developmental signal. Behav. Brain Res. 73, 19-29; Ugrumov, M.V., 1997. Hypothalamic monoaminergic systems in ontogenesis: development and functional significance. Int. J. Dev. Biol. 41, 809-816]. This study was aimed to test whether it provides long-lasting effects on the differentiating vasoactive intestinal polypeptide (VIP) and vasopressin (VP) neurons of the suprachiasmatic nucleus (SCN) in rats. To this aim, 5-HT was depleted in fetal brain by daily injections of p-chlorophenylalanine (pCPA), an inhibitor of 5-HT synthesis, to pregnant rats from the 13th to the 21st day of gestation. Pregnant rats injected with saline served as controls. The offsprings (males) of pCPA-treated and control pregnant rats were maintained after birth for two months under normal laboratory conditions. Then, the SCN was processed for immunocytochemistry of VIP and VP and in situ hybridization of appropriate mRNAs. There were no differences in concentrations of VIP and VP mRNAs in the SCN in adult offsprings of the 5-HT-depleted pregnant rats compared to the controls. Moreover, 5-HT deficiency did not induce any change in size of VIP-immunoreactive (IR) and VP-IR neurons. Conversely, both the numbers of VIP- and VP-immunoreactive neurons and concentrations of the peptides in cell bodies increased significantly. It is concluded that 5-HT provides long-lasting effects on differentiating VIP and VP neurons in the SCN resulting in attenuated release rather than elevated synthesis of both peptides in adulthood.
The morphogenetic influences of serotonin on the differentiation of neurons synthesizing vasoactive intestinal polypeptide (VIP) in the suprachiasmatic nucleus were studied in rats. This was addressed by comparative morphofunctional analysis of VIP neurons in adult rats whose brains developed prenatally in conditions of normal and deficient serotonin metabolism. Serotonin deficiency was created in fetuses by treatment of their mothers with p-chlorophenylalanine (PCPA). Pregnant females in controls were treated with 0.9% NaCl. VIP neurons in experimental and control animals were found to show no differences in VIP mRNA concentrations and, probably, in the level of VIP synthesis. However, inhibition of serotonin synthesis led to an increase in the number of VIP-immunoreactive neurons and an increase in the VIP concentration within these cells. This was not associated with any change in neuron size, which was an indicator of the absence of functional hypertrophy accompanying activation of specific synthesis. Comparison of the data obtained here showed that during prenatal ontogenesis, serotonin has an imprinting influence on the differentiation of VIP neurons and is probably involved in the formation of the mechanism of VIP secretion.
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