Glial cell line-derived neurotrophic factor reverses toxin-induced injury to midbrain dopaminergic neurons in vivo.
Fischer 344 rats were unilaterally injected into the medial forebrain bundle with 6-hydroxydopamine (6-OHDA). Apomorphine-induced rotational behavior was used to select animals whose rotation exceeded 300 turns/h, corresponding to greater than 95% dopamine (DA) depletion in the ipsilateral striatum. Four weeks later, glial cell line-derived neurotrophic factor (GDNF) or vehicle was injected intranigrally ipsilateral to the lesion (0.1-100 micrograms). The highest dose of GDNF tested produced a marked decrease in rotational behavior. This dose also produced levels of DA in the ipsilateral substantia nigra (SN) which were not statistically different from the contralateral side. Vehicle-treated animals showed a marked DA depletion in the ipsilateral SN. These results demonstrate neurochemical and behavioral improvements in unilaterally DA-lesioned rats following intranigral administration of GDNF, suggesting that GDNF may develop into a useful therapy for Parkinson's disease.
Hoffer
B J
BJ
University of Colorado Health Sciences Center, Denver 80262.
Hoffman
A
A
Bowenkamp
K
K
Huettl
P
P
Hudson
J
J
Martin
D
D
Lin
L F
LF
Gerhardt
G A
GA
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007267:Injections; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000473:pathology; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects*; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012399:Rotation; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000502:physiology
D009414:Nerve Growth Factors; D016627:Oxidopamine; D004298:Dopamine