Intracerebral xenografts of human mesencephalic tissue into athymic rats: Immunochemical and in vivo electrochemical studies

Intracerebral allografts of fetal neurons have been studied in both rodents and nonhuman primates. Such research has been directed towards problems in developmental neurobiology and in animal models of neurological diseases. Whether intracerebrally transplanted human fetal neurons are capable of forming synapses and releasing neurotransmitters are key questions in any application of this approach to human brain development and dysfunction. We studied these questions by examining the immunocytochemical and in vivo electrochemical properties of xenografts of human mesencephalic dopaminergic neurons placed into athymic 'nude' rats. The transplanted neurons survive, continue to express human-specific Thy-1 immunoreactivity, and extend neuronal processes into the host brain where morphologically identifiable synapses form. Potassium-evoked release of monoamines occurs in the vicinity of the graft but is absent in more remote areas of the host neuropil. These results indicate that human fetal tissue fragments can provide a source of viable neuroblasts for transplantation. Further, synapses form between pre- and postsynaptic elements expressing different species-specific cell surface markers; thus, these markers do not play a determining role in synaptogenesis.