BRAIN-DERIVED NEUROTROPHIC FACTOR ENHANCES FUNCTION RATHER THAN SURVIVAL OF INTRASTRIATAL DOPAMINE CELL-RICH GRAFTS

Brain-derived neurotrophic factor (BDNF) has been shown to promote the survival of dopaminergic neurons from the substantia nigra in cell cu lture. In order to assess whether a similar survival-promoting effect is present also in vivo, we grafted fetal nigral tissue to the dopamin e-depleted striatum of 6-hydroxydopamine-lesioned rats receiving two-w eek intraventricular infusions or daily intrastriatal injections of BD NF, NGF, or vehicle. When infused chronically at a high dose (12 mug/d ay) into the lateral ventricle, BDNF caused a behavioral syndrome of r educed food and water intake, body weight loss, and locomotor hyperact ivity in comparison to NGF- and vehicle-infused graft recipients. NGF- infused graft recipients displayed a transient weight loss during the first week of infusion. At 15 days, amphetamine-induced turning was si gnificantly attenuated to 3% of pregraft values in BDNF-infused recipi ents, whereas functional graft effects were not present in NGF- or veh icle-infused animals. Survival of tyrosine hydroxylase-immunoreactive graft cells, however, was similar in all treatment groups. Notably, NG F- and BDNF-infusions led to a significant size increase of cholinergi c host neurons in the medial septal nucleus and the vertical limb of t he diagonal band ipsilateral to the infusion, wheras there was no chol inergic neuron hypertophy in vehicle-infused animals. Daily intrastria tal injections of BDNF (2 mug) produced no weight loss or locomotor hy peractivity, but also enhanced functional graft effects in BDNF-inject ed, as compared to vehicle-injected animals. Survival rates of grafted tyrosine hydroxylase-immunoreactive cells were, however, similar in b oth groups. We conclude that, using the administration methods chosen for this study, BDNF may enhance the functional capacity but not the s urvival of grafted dopamine neurons.