Diminished survival of mesencephalic dopamine neurons grafted into aged hosts occurs during the immediate postgrafting interval

The survival rate of dopamine (DA) neurons in mesencephalic grafts to young adult rats is poor, estimated at 5-20%, and even poorer in grafts to the a ged striatum. Grafted cells die in young adult rats during the first 4 days after implantation. The present study was undertaken to determine whether the decreased survival of DA neurons in grafts to aged rats is (1) due to a dditional cell death during the immediate postgrafting interval or (2) due to protracted cell loss during longer postgrafting intervals. We compared s urvival rates of tyrosine hydroxylase-immunoreactive (THir) neurons in cell suspension grafts to young adult (3 months) and aged (24 months) male Fisc her 344 rats at 4 days and 2 weeks after transplantation. At 4 days after g rafting, mesencephalic grafts within the aged rat striatum contain approxim ately 25% of the number of THir neurons in the same mesencephalic cell susp ension grafted to young adult rats. This corroborates the decreased surviva l of grafted DA neurons we have demonstrated previously at 10 weeks postgra fting. THir neurons in grafts to the intact striatum possessed a significan tly shorter "long axis" than their counterparts on the lesioned side. No si gnificant differences in the number of apoptotic nuclear profiles or total alkaline phosphatase staining between mesencephalic grafts to young and age d rats were detectable at 4 days postgrafting, In summary, the present stud y indicates that the exaggerated cell death of grafted DA neurons that occu rs following implantation to the aged striatum occurs during the immediate postgrafting interval, timing identical to that documented for young adult hosts. (C) 2001 Academic Press.