Manganese induced brain lesions in Macaca fascicularis as revealed by positron emission tomography and magnetic resonance imaging.
A series of positron emission tomography scans was made on two monkeys during a 16-month period when they received manganese(IV)oxide by subcutaneous injection. The distribution of [11C]-nomifensine uptake, indicating dopamine terminals, was followed in both monkey brains. The brain distributions of [11C]-raclopride, demonstrating D2 dopamine receptors, and [11C]-L-dopa, as a marker of dopamine turnover, were followed in one monkey each. The monkeys developed signs of poisoning namely unsteady gait and hypoactivity. The [11C]-nomifensine uptake in the striatum was reduced with time and reached a 60% reduction after 16 months exposure. This supports the suggestion that dopaminergic nerve endings degenerate during manganese intoxication. The [11C]-L-dopa decarboxylation was not significantly altered indicating a sparing of [11C]-L-dopa decarboxylation during manganese poisoning. A transient decrease of [11C]-raclopride binding occurred but at the end of the study D2-receptor binding had returned to starting values. The magnetic resonance imaging (MRI) revealed that the manganese accumulated in the globus pallidus, putamen and caudate nucleus. There were also suggestions of gliosis/edema in the posterior limb of the internal capsule. MRI might be useful to follow manganese intoxication in humans as long as the scan is made within a few months of exposure to manganese, i.e. before a reversal of the manganese accumulation.
Eriksson
H
H
Department of Neurochemistry and Neurotoxicology, Stockholm University, Sweden.
Tedroff
J
J
Thuomas
K A
KA
Aquilonius
S M
SM
Hartvig
P
P
Fasth
K J
KJ
Bjurling
P
P
Långström
B
B
Hedström
K G
KG
Heilbronn
E
E
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D065127:Dopamine D2 Receptor Antagonists; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D017895:Manganese Compounds; D020149:Manganese Poisoning; D009627:Nomifensine / Q000378:metabolism; D010087:Oxides; D020891:Raclopride; D011859:Radiography; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012457:Salicylamides / Q000378:metabolism; D014055:Tomography, Emission-Computed
D065127:Dopamine D2 Receptor Antagonists; D017895:Manganese Compounds; D010087:Oxides; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D009627:Nomifensine; D020891:Raclopride; C027424:manganese oxide; D004298:Dopamine