Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain.
Glial-cell-line-derived neurotrophic factor (GDNF) promotes survival of embryonic dopaminergic neurons in culture, and its expression pattern suggests a role as a transient target-derived trophic factor for dopaminergic neurons of the substantia nigra. These neurons participate in the control of motor activity, emotional status and cognition, and they degenerate in Parkinson's disease for unknown reasons. To test whether GDNF has a trophic effect on dopaminergic neurons in the adult brain, we used a rat model in which these neurons are induced to degenerate by transecting their axons within the medial forebrain bundle. We report here that axotomy resulted in loss of half the tyrosine hydroxylase-expressing neurons in the substantia nigra. This loss was largely prevented by repeated injections of GDNF adjacent to the substantia nigra. Our findings suggest that GDNF or related molecules may be useful for the treatment of Parkinson's disease.
Department of Neuroscience, Genentech Inc., South San Francisco, California 94080.
K D
KD
Beck
J
J
Valverde
T
T
Alexi
K
K
Poulsen
B
B
Moffat
R A
RA
Vandlen
A
A
Rosenthal
F
F
Hefti
D000818:Animals; D001369:Axons; D001927:Brain Diseases / Q000188:drug therapy / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects; D003714:Denervation; D004298:Dopamine / Q000378:metabolism*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009410:Nerve Degeneration / Q000187:drug effects*; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine