Autoradiographic localization and density of [125I]ferrotransferrin binding sites in the basal ganglia of control subjects, patients with Parkinson's disease and MPTP-lesioned monkeys.
Degeneration of the nigro-striatal dopaminergic neurons occurring in Parkinson's disease is associated with an increase in iron concentrations in the substantia nigra. As this metal catalyzes the production of free radicals, and oxidative stress may participate in the cascade of events ending in cell death, this increase in iron content may be involved in dopaminergic neuronal death. The localization and number of receptors for transferrin were investigated postmortem by quantitative autoradiography of iodinated-ferrotransferrin binding in the basal ganglia from controls, parkinsonian patients and MPTP-lesioned monkeys. In human controls, specific [125i] ferrotransferrin binding-site density was highest in the putamen and the caudate nucleus, and lowest in the globus pallidus. In parkinsonian patients, it was increased in the putamen and caudate nucleus, while in MPTP-intoxicated monkeys, there was a tendency for levels to decrease in these two regions. An inverse relationship between binding density and iron content reported in the studied regions supports the assumption of a possible capture of iron at the level of dopaminergic terminals and, in parkinsonian patients, on other cellular elements as well. These results suggest an involvement of transferrin receptors in iron uptake in the striatum of patients with Parkinson's disease, with differences between the 'acute' nigro-striatal MPTP-induced degeneration syndrome and the chronic long lasting human disease.
Faucheux
B A
BA
Laboratoire de Médecine Expérimentale, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, INSERM U289, Hôpital de la Salpêtrière, Paris, France.
Herrero
M T
MT
Villares
J
J
Levy
R
R
Javoy-Agid
F
F
Obeso
J A
JA
Hauw
J J
JJ
Agid
Y
Y
Hirsch
E C
EC
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001345:Autoradiography; D001479:Basal Ganglia / Q000737:chemistry*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D006801:Humans; D007457:Iodine Radioisotopes; D007980:Levodopa / Q000627:therapeutic use*; D008252:Macaca fascicularis; D009410:Nerve Degeneration / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism*; D011869:Radioligand Assay; D011990:Receptors, Transferrin / Q000032:analysis*; D012016:Reference Values
D007457:Iodine Radioisotopes; D011990:Receptors, Transferrin; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine