BDNF ENHANCES THE FUNCTIONAL REINNERVATION OF THE STRIATUM BY GRAFTEDFETAL DOPAMINE NEURONS

Transplantation of fetal dopaminergic neurons to the striatum can amel iorate neurological deficits exhibited by experimental animals and hum an graft recipients with Parkinson's disease. Recovery, however, is in complete due to suboptimal survival of grafted cells and limited synap tic integration with the host brain. A number of neurotrophic factors have recently been shown to promote the survival and differentiation o f dopamine neurons in vitro. In the present study we examined the effe cts of one such factor, brain-derived neurotrophic factor (BDNF), on t he development of fetal substantia nigra following transplantation to the dopamine-depleted striatum of adult rats. Infusion of BDNF greatly enhanced the reinnervation of the host striatum by the engrafted dopa mine neurons, as determined by tyrosine hydroxylase immunostaining, an d also increased the effect of the graft on locomotor behavior induced by amphetamine administration. These effects became apparent during t he 4-week period of BDNF infusion and persisted for an additional 6 we eks following the termination of BDNF delivery. These findings demonst rate that BDNF exerts a significant effect on the functional reinnerva tion of the striatum by transplanted fetal dopamine neurons in the rat , and suggest that application of this factor might similarly improve the clinical efficacy of neural transplantation employed in the treatm ent for Parkinson's disease. (C) 1996 Academic Press, Inc.