GLIAL-CELL LINE-DERIVED NEUROTROPHIC FACTOR IMPROVES SURVIVAL OF DOPAMINERGIC-NEURONS IN TRANSPLANTS OF FETAL VENTRAL MESENCEPHALIC TISSUE

This study was designed to determine whether or not an exogenous sourc e of glial cell line-derived neurotrophic factor (GDNF) could be deliv ered continuously into the denervated/transplanted striatum and stimul ate the survival, growth, and function of fetal ventral mesencephalic tissue transplants. Adult male rats with unilateral g-hydroxydopamine lesions received transplants of fetal ventral mesencephalic tissue int o the denervated striatum. Immediately thereafter, osmotic pumps [Alze t 2002, 0.5 mu l/h] were attached to intracerebral cannula and either a citrate buffer alone [control] or r-methuGDNF [dissolved in sodium c itrate buffer to a concentration of 0.45 mu g/mu l] was infused into a site similar to 1.0 mm lateral to the transplant for a 2-week period; one group of lesioned animals did not receive transplants but was inf used with GDNF. The effect of GDNF on tyrosine hydroxylase-positive (T H+) fiber out-growth from transplants was variable, and image analysis revealed no significant difference between the GDNF and citrate group s. In contrast, the mean number of TH+ cells bodies in transplants inf used with GDNF [2,037 +/- 149, n = 8] vs citrate [663 +/- 1.60, n = 8] was statistically significant (P < 0.001); cell counts were made in e very third brain section [35 mu m]. Similarly, transplants infused wit h GDNF showed an overcompensatory effect to amphetamine-induced rotati onal behavior that was significantly lower than that observed in trans planted animals receiving citrate buffer infusions. Infusions of GDNF into the denervated striatum alone had no significant effect on amphet amine-induced rotational behavior or on TH fiber morphology in the les ioned striatum. Thus, a continuous infusion of GDNF can improve the su rvivability of dopaminergic neurons in transplants of fetal ventral me sencephalic tissue. (C) 1998 Academic Press.