Denervation of serotonergic fibers in the hippocampus induced a trophic factor which enhances the maturation of transplanted serotonergic neurons but not norepinephrine neurons.

The trophic effects of specific denervation on the growth and survival of fetal serotonergic (5-HT) or norepinephrinergic (NE) neurons grafted into the hippocampus were assessed by means of two transplantation paradigms. In the first, fetal raphe cells (containing 5-HT neurons) were transplanted into the control hippocampus. In the second, the transplantation was performed 2 weeks after the specific removal of 5-HT afferents to the hippocampus with 5,7-dihydroxytryptamine (5,7-DHT). We found that a month after transplantation, the number of 5-HT immunoreactive neurons was not significantly different between the two experimental paradigms. However, transplanted raphe neurons had 400% more 5-HT synaptosomal high-affinity uptake and 380% higher content of 5-HT in the hippocampus with prior 5,7-DHT lesion than in control hippocampus. Furthermore, immunocytochemistry showed that the transplanted 5-HT neurons had denser processes and varicosities in the hippocampus with lesion than in control hippocampus. The somatic area of the neurons with these denser processes and varicosities was 42% larger than that of control group. A greater 5-HT level could be achieved if transplanted neurons in the control hippocampus were treated with the supernatant extracted from the hippocampus with 5,7-DHT lesion. In contrast, the NE level of the implanted fetal locus ceruleus (containing NE neurons) was not significantly higher in the 5-HT denervated hippocampus than in control hippocampus a month after transplantation. These results suggest that 5-HT denervation in the hippocampus induces a trophic substance which promotes the maturation rather than survival of 5-HT neurons but not NE neurons.