Sham transplantation protects against 6-hydroxydopamine-induced dopaminergic toxicity in rats: behavioral and morphological evidence.
Administration of the neurotoxin 6-hydroxydopamine (6-OHDA) to rat brain causes biochemical and neuroanatomical changes to the nigrostriatal dopaminergic pathway similar to those observed in Parkinson's disease (PD). Although the cause of PD is unknown, it has been hypothesized that the neurodegenerative changes seen in PD might result from exposure to a neurotoxin. Therefore, strategies for limiting neurotoxin-induced dopaminergic damages, like those caused by 6-OHDA, may be of both clinical and basic interest. Accordingly, we tested the ability of both fetal neural (striatum) and fetal non-neural (liver) tissue implants to protect the rat striatum against the toxic effects of a subsequent intrastriatal injection of 6-OHDA. Non-grafted rats (lesion only) showed amphetamine-induced rotational behavior and a decrease in striatal [3H]mazindol-labeled dopamine uptake sites after 6-OHDA injection. In contrast, the animals grafted with striatum or liver showed no behavioral or biochemical changes. Interestingly, sham-transplanted control animals were also protected against the 6-OHDA-induced toxicity. These results suggest that the resistance of the dopaminergic system against 6-OHDA neurotoxicity observed in grafted and sham-transplanted animals is likely to be related to the surgical procedure itself. This observation points to a possible role for surgery-related events in the clinical improvement described in PD patients who underwent intracerebral transplantation.
Przedborski
S
S
Laboratory of Preclinical Neurosciences, Columbia University, College of Physicians and Surgeons, New York, New York 10032.
Levivier
M
M
Kostic
V
V
Jackson-Lewis
V
V
Dollison
A
A
Gash
D M
DM
Fahn
S
S
Cadet
J L
JL
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D001552:Benzazepines / Q000378:metabolism; D016380:Brain Tissue Transplantation / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000502:physiology* / Q000637:transplantation; D004298:Dopamine / Q000378:metabolism; D005260:Female; D016332:Fetal Tissue Transplantation / Q000502:physiology; D006892:Hydroxydopamines / Q000037:antagonists & inhibitors / Q000633:toxicity*; D016031:Liver Transplantation / Q000502:physiology*; D008454:Mazindol / Q000378:metabolism; D016627:Oxidopamine; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism; D017447:Receptors, Dopamine D1; D013239:Stereotyped Behavior / Q000187:drug effects; D016042:Transplantation, Heterotopic; D014316:Tritium
D001552:Benzazepines; D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D014316:Tritium; D016627:Oxidopamine; D008454:Mazindol; D004298:Dopamine