RT Journal Article
SR Electronic
T1 Glial Cell Line-Derived Neurotrophic Factor Is Essential for Postnatal Survival of Midbrain Dopamine Neurons
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3182
OP 3190
DO 10.1523/JNEUROSCI.20-09-03182.2000
VO 20
IS 9
A1 Ann-Charlotte Granholm
A1 Mary Reyland
A1 David Albeck
A1 Linda Sanders
A1 Greg Gerhardt
A1 George Hoernig
A1 Liya Shen
A1 Heiner Westphal
A1 Barry Hoffer
YR 2000
UL http://www.jneurosci.org/content/20/9/3182.abstract
AB Glial cell line-derived neurotrophic factor (GDNF) is one of the most potent trophic factors that have been identified for midbrain dopamine (DA) neurons. Null mutations for trophic factor genes have been used frequently for studies of the role of these important proteins in brain development. One problem with these studies has been that often only prenatal development can be studied because many of the knockout strains, such as those with GDNF null mutations, will die shortly after birth. In this study, we looked at the continued fate of specific neuronal phenotypes from trophic factor knockout mice beyond the time that these animals die. By transplanting fetal neural tissues from GDNF −/−, GDNF +/−, and wild-type (WT) mice into the brain of adult wild-type mice, we demonstrate that the continued postnatal development of ventral midbrain dopamine neurons is severely disturbed as a result of the GDNF null mutation. Ventral midbrain grafts from −/− fetuses have markedly reduced DA neuron numbers and fiber outgrowth. Moreover, DA neurons in such transplants can be “rescued” by immersion in GDNF before grafting. These findings suggest that postnatal survival and/or phenotypic expression of ventral mesencephalic DA neurons is dependent on GDNF. In addition, we present here a strategy for studies of maturation and even aging of tissues from trophic factor and other knockout animals that do not survive past birth.