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

Publisher Website
Google Scholar
Abstract
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‐dihy‐droxytryptamine (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.