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.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000320:Adrenergic Fibers / Q000502:physiology; D000818:Animals; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008125:Locus Coeruleus / Q000196:embryology*; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009638:Norepinephrine / Q000502:physiology*; D011903:Raphe Nuclei / Q000196:embryology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*; D009435:Synaptic Transmission
D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D009638:Norepinephrine