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 potent neurotrophic factor for dopamine neurons in culture and to prevent the loss of substantia nigra dopamine neurons following in vivo lesions with 6-hydroxydopamine (6-OHDA). In this study we used mesencephalic cultures containing both neurons and glia to examine whether GDNF protects dopamine neurons from 6-OHDA toxicity in vitro. Our data show that GDNF does not prevent the loss of dopamine neurons caused by treatment with 6-OHDA in vitro. However, continuous exposure to GDNF increases the high affinity dopamine uptake in cultures treated with 6-OHDA, suggesting that it enhances the growth of damaged dopamine neurons. We also show that in vitro treatment with 6-OHDA causes widespread cell death in mesencephalic cultures, which is not restricted to dopamine neurons. The lack of selectivity of 6-OHDA toxicity when applied in vitro may explain the inability of GDNF to prevent the loss of dopamine neurons in mesencephalic cultures. The stimulation of the growth of 6-OHDA damaged dopamine neurons by GDNF, observed in our study, suggests that it may prove beneficial in the treatment of injured dopamine neurons.
Kramer
B C
BC
Fishberg Center for Neurobiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Goldman
A D
AD
Mytilineou
C
C
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008636:Mesencephalon / Q000187:drug effects* / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D018663:Adrenergic Agents; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016627:Oxidopamine; D004298:Dopamine