SURVIVAL OF NIGRAL GRAFTS WITHIN THE STRIATUM OF MARMOSETS WITH 6-OHDA LESIONS DEPENDS CRITICALLY ON DONOR EMBRYO AGE

The study examined the importance of embryonic donor age for the survi val of nigral grafts in 6-OHDA-lesioned marmosets. The issue as to whe ther donor age is critical for the survival of nigral grafts in primat es is controversial, because several early reports suggested that rela tively old tissue could survive transplantation and produce functional benefits in monkeys, in contrast to the restrictive time dependence o bserved in rodents. Embryonic marmoset donors embryos of three differe nt ages were employed: 1) E74 (Carnegie stage 18-19); 2) E83-84 (Carne gie stage 23+); 3) E92-93 (foetal period). The nigral neurons derived from the ventral mesencephalon in the two older donor age groups did n ot survive well when grafted to the striatum of adult marmosets with u nilateral 6-OHDA lesions. Although a few tyrosine hydroxylase (TH+) ne urons could be identified by immunohistochemistry at graft sites in al l recipients in older donor age groups, the numbers of surviving neuro ns in these were small, on average typically less than 100 TH+ cells. These small grafts were not sufficient to affect amphetamine-induced r otation. In contrast, many more TH+ cells typically survived transplan tation In the recipients of graft tissue derived from the youngest don ors and amphetamine-induced rotation was significantly reduced in this group alone. The time course and extent of the reduction in rotation was remarkably similar to that observed in previous marmoset nigral gr aft studies, confirming the utility of amphetamine-induced rotation as a sensitive and reliable indicator of nigral graft function in this s pecies. Considering these results and other recent evidence from monke y to monkey, human to rat, and human to human graft studies, the survi val of embryonic nigral tissues derived from primate donors transplant ed into the striatum does appear to be critically dependent on the age of the donor tissue. (C) 1997 Elsevier Science Inc.