Quantitative autoradiographic distribution of [3H]mazindol-labeled dopamine uptake sites in the brains of superoxide dismutase transgenic mice.
Superoxide dismutase (SOD) is an important enzyme which is involved in the dismutation of the toxic radical, superoxide anion. The activity of CuZnSOD is increased in patients who suffer from Down's Syndrome, Alzheimer's disease, and in Parkinson's disease. In order to evaluate the contribution of this enzyme to the neuropathology of these neurodegenerative diseases, transgenic mice have been constructed which express the human CuZnSOD gene. As a first step towards exploring these issues, we have carried out an autoradiographic binding study of the distribution of the catecholaminergic uptake blocker mazindol in the brain of these transgenic mice and of their littermates. Desmethylimipramine (DMI)-insensitive [3H]mazindol binding sites which correspond to dopamine uptake sites were located in the striatum, the nucleus accumbens, the olfactory tubercle and in the substantia nigra. Within the striatum, there was a lateromedial gradient, with higher concentration of dopamine uptake sites being found laterally. These findings suggest that subregions of the basal ganglia may be more susceptible to the deleterious effects of dopaminotoxic drugs which are taken up into the dopaminergic neurons via these uptake sites. Saturation experiments revealed no differences in the characteristics of [3H]mazindol binding sites between the two groups of mice. Thus, increased activity of SOD is not associated with diffuse changes in the molecular structures of receptors in mice brain.
Cadet
J L
JL
Department of Neurology, Columbia University, College of Physicians and Surgeons, New York, NY 10032.
Przedborski
S
S
Kostic
V
V
Jackson-Lewis
V
V
Carlson
E
E
Epstein
C J
CJ
D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry / Q000187:drug effects*; D002421:Caudate Nucleus / Q000033:anatomy & histology / Q000201:enzymology; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D006801:Humans; D008454:Mazindol; D051379:Mice; D008822:Mice, Transgenic; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000201:enzymology; D011699:Putamen / Q000033:anatomy & histology / Q000201:enzymology; D011954:Receptors, Dopamine / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D011954:Receptors, Dopamine; D004295:Dihydroxyphenylalanine; D008454:Mazindol; D013482:Superoxide Dismutase