Glial cell line-derived neurotrophic factor is essential for postnatal survival of midbrain dopamine neurons

Citation
Ac. Granholm et al., Glial cell line-derived neurotrophic factor is essential for postnatal survival of midbrain dopamine neurons, J NEUROSC, 20(9), 2000, pp. 3182-3190
Citations number
46
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE
ISSN journal
0270-6474 → ACNP
Volume
20
Issue
9
Year of publication
2000
Pages
3182 - 3190
Database
ISI
SICI code
0270-6474(20000501)20:9<3182:GCLNFI>2.0.ZU;2-B
Abstract
Glial cell line-derived neurotrophic factor (GDNF) is one of the most poten t trophic factors that have been identified for midbrain dopamine (DA) neur ons. Null mutations for trophic factor genes have been used frequently for studies of the role of these important proteins in brain development. One p roblem with these studies has been that often only prenatal development can be studied because many of the knockout strains, such as those with GDNF n ull mutations, will die shortly after birth. In this study, we looked at th e continued fate of specific neuronal phenotypes from trophic factor knocko ut mice beyond the time that these animals die. By transplanting fetal neur al tissues from GDNF -/-, GDNF +/-, and wild-type (WT) mice into the brain of adult wild-type mice, we demonstrate that the continued postnatal develo pment of ventral midbrain dopamine neurons is severely disturbed as a resul t of the GDNF null mutation. Ventral midbrain grafts from -/- fetuses have markedly reduced DA neuron numbers and fiber outgrowth. Moreover, DA neuron s in such transplants can be "rescued" by immersion in GDNF before grafting . These findings suggest that postnatal survival and/or phenotypic expressi on of ventral mesencephalic DA neurons is dependent on GDNF. In addition, w e present here a strategy for studies of maturation and even aging of tissu es from trophic factor and other knockout animals that do not survive past birth.