BDNF enhances the functional reinnervation of the striatum by grafted fetal dopamine neurons

Transplantation of fetal dopaminergic neurons to the striatum can ameliorate neurological deficits exhibited by experimental animals and human graft recipients with Parkinson's disease. Recovery, however, is incomplete due to suboptimal survival of grafted cells and limited synaptic integration with the host brain. A number of neurotrophic factors have recently been shown to promote the survival and differentiation of dopamine neurons in vitro. In the present study we examined the effects of one such factor, brain-derived neurotrophic factor (BDNF), on the 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 dopamine neurons, as determined by tyrosine hydroxylase immunostaining, and also increased the effect of the graft on locomotor behavior induced by amphetamine administration. These effects became apparent during the 4-week period of BDNF infusion and persisted for an additional 6 weeks following the termination of BDNF delivery. These findings demonstrate that BDNF exerts a significant effect on the functional reinnervation 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 treatment for Parkinson's disease. (C) 1996 Academic Press, Inc.