Glial cell line derived neurotrophic factor promotes the recovery of dopamine neurons damaged by 6-hydroxydopamine in vitro

Glial cell line derived neurotrophic factor (GDNF) has been shown to be a p otent neurotrophic factor for dopamine neurons in culture and to prevent th e loss of substantia nigra dopamine neurons following in vivo lesions with 6-hydroxydopamine (6-OHDA). In this study we used mesencephalic cultures co ntaining both neurons and glia to examine whether GDNF protects dopamine ne urons from 6-OHDA toxicity in vitro. Our data show that GDNF does not preve nt the loss of dopamine neurons caused by treatment with 6-OHDA in vitro. H owever, continuous exposure to GDNF increases the high affinity dopamine up take in cultures treated with 6-OHDA, suggesting that it enhances the growt h of damaged dopamine neurons. We also show that in vitro treatment with 6- OHDA causes widespread cell death in mesencephalic cultures, which is not r estricted to dopamine neurons. The lack of selectivity of 6-OHDA toxicity w hen applied in vitro may explain the inability of GDNF to prevent the loss of dopamine neurons in mesencephalic cultures. The stimulation of the growt h of 6-OHDA damaged dopamine neurons by GDNF, observed in our study, sugges ts that it may prove beneficial in the treatment of injured dopamine neuron s. (C) 1999 Elsevier Science B.V. All rights reserved.