GDNF induces recovery of the nigrostriatal dopaminergic system in the rat brain following intracerebroventricular or intraparenchymal administration

Background. Glial cell line-derived neurotrophic factor (GDNF) has been shown to be a survival and neuroprotective factor for nigrostriatal dopaminergic neurons in vivo. The present study was designed to investigate the possible neuroprotective and restorative role by GDNF for dopaminergic neurons which were exposed to the neurotoxin 6-hydroxydopamine (6-OHDA). Method. We compared neurochemical, morphological and behavioural changes following striatal infusion of GDNF to those following intracerebroventricular (i.c.v.) infusion. Findings. Apomorphine-induced rotation showed significant recovery after both types of infusion. Significant recovery of tyrosine hydroxylase (TH)-immunoreactive (IR) neurons and fibers were found in the substantia nigra and striatum following both striatum and i.c.v. infusion except for the number of TH-IR neurons in the i.c.v. infusion group. Interpretation. These results suggest that GDNF induces recovery of the nigrostriatal dopaminergic system, and this indicates a potential usefulness of GDNF for the treatment of Parkinson's disease.