Stimulation of serotonergic neuronal maturation after fetal mesencephalic raphe transplantation into the 5,7-DHT-lesioned hippocampus of the adult rat.
Neurotoxin lesioning of 5-HT fibers selectively induced the homotypic collateral sprouting of spared 5-HT fibers in the hippocampus. We have used this model to investigate the possibility that the neurotoxin-primed hippocampus will enhance the development of transplanted fetal serotonergic neurons in the brain. The neurotoxin 5,7-DHT, when microinjected into the FF, produced a specific and partial depletion of 5-HT in the hippocampus of adult rats. The ability of the 5,7-DHT-primed hippocampus to selectively support the neurochemical maturation of fetal serotonergic cells was tested by assaying the transplanted fetal raphe or LC 1 month after neuronal transplantation. The neurochemical maturation of fetal 5-HT and NE neurons was dramatically different when they were transplanted in the 5,7-DHT-FF-lesioned hippocampus as compared to the normal hippocampus. The transplanted 5-HT neurons had 480% more SHAU of [3H]5-HT and had a 250% greater content of 5-HT in the partially denervated hippocampus than in the normal hippocampus after 1 month. Furthermore, extracts obtained from lesioned hippocampus enhanced the 5-HT content of 5-HT neurons transplanted in the normal hippocampus, to a level similar to that seen in neurons transplanted in the lesioned hippocampus. In contrast, the implanted NE neurons of fetal LC had a lower NE level in the 5-HT partially denervated hippocampus than in normal hippocampus after 1 month in the host site. The growth of the NE transplants was not facilitated by the vacant postsynaptic space produced by the 5,7-DHT lesion. These results suggest that the 5-HT denervation triggered a trophic signal selectively enhancing the development of the 5-HT neurons but not the NE neurons. Our results are consistent with previous studies showing homotypic collateral sprouting in 5,7-DHT-primed hippocampus.
D015116:5,7-Dihydroxytryptamine / Q000633:toxicity*; D000818:Animals; D004102:Dihydroxytryptamines / Q000633:toxicity*; D005260:Female; D005333:Fetus; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000502:physiology*; D011903:Raphe Nuclei / Q000637:transplantation*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D004102:Dihydroxytryptamines; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase