GDNF induces a dystonia-like state in neonatal rats and stimulates dopamine and serotonin synthesis.
To test whether glial cell line-derived neurotrophic factor (GDNF) regulates the development of nigral dopaminergic neurons in vivo, neonatal rats received bilateral injections of GDNF into the striatum. Injections at postnatal day 2 induced a unique transient behavioral pattern characterized by forelimb hyperflexure, clawed toes of all limbs, and a kinked tail. Parallel to the behavioral changes, the levels of striatal and ventral mesencephalic dopamine and serotonin were increased from 60% to 100% with a proportional increase of principal metabolite levels. GDNF increased tyrosine hydroxylase activity in the ventral mesencephalon, but did not affect striatal activity of choline acetyltransferase and GABA uptake. GDNF failed to induce sprouting of dopaminergic neurites. Our findings suggest that during development striatal GDNF regulates the capacity of dopaminergic and of serotonergic neurons for neurotransmitter production and release.
Beck
K D
KD
Department of Neuroscience, Genentech Incorporated, South San Francisco, California 94080, USA.
Irwin
I
I
Valverde
J
J
Brennan
T J
TJ
Langston
J W
JW
Hefti
F
F
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000097:blood* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004421:Dystonia / Q000145:classification*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007150:Immunohistochemistry; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000097:blood* / Q000378:metabolism; D014018:Tissue Distribution
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012701:Serotonin; D004298:Dopamine