GROWTH-FACTORS IMPROVE IMMEDIATE SURVIVAL OF EMBRYONIC DOPAMINE NEURONS AFTER TRANSPLANTATION INTO RATS

Embryonic dopamine neurons survive poorly after transplant into models of Parkinson's disease, possibly due to programmed cell death (apopto sis), Apoptosis in cultured dopamine neurons can be reduced by growth factors such as glial cell line-derived neurotrophic factor (GDNF) or a combination of insulin-like growth factor-I (IGF-I) and basic fibrob last growth factor (bFGF). To improve the survival of dopamine neurons in grafts, strands of E15 rat ventral mesencephalon were pretreated w ith a combination of GDNF, IGF-I, and bFGF and then transplanted into 6-hydroxydopamine-lesioned rats. In control animals, only 32% of dopam ine neuron profiles survived the first 24 h after transplant. Growth f actor pretreatment increased survival to 49% on day 1. Growth factors reduced the apoptotic rate of transplanted cells, just as they had in the previous in vitro experiments. Apoptotic nuclear morphology was ob served in the transplanted dopamine neurons. We conclude that the majo rity of transplanted dopamine neurons die in grafts within the first 2 4 h after transplant, most likely by an apoptotic mechanism. Preventio n of apoptosis with anti-apoptotic agents may improve the viability of dopamine neurons grafted for Parkinson's disease. (C) 1998 Elsevier S cience B.V.