MANGANESE INTOXICATION IN THE RHESUS-MONKEY - A CLINICAL, IMAGING, PATHOLOGICAL, AND BIOCHEMICAL-STUDY

We gave three adult rhesus monkeys seven IV injections of manganese ch loride at similar to 1-week intervals, We evaluated neurologic status by serial clinical examinations and performed a levodopa test if the a nimal developed features of basal ganglia dysfunction. After the anima ls were killed, we performed neuropathologic, neurochemical, and laser microprobe mass analysis (LAMMA) studies. Two of three animals develo ped a parkinsonian syndrome characterized by bradykinesia, rigidity, a nd facial grimacing suggestive of dystonia but not tremor. Neither ani mal responded to levodopa. Autopsy demonstrated gliosis primarily conf ined to the globus pallidus (GP) and the substantia nigra pars reticul aris (SNr), We detected focal mineral deposits throughout the GP and S Nr, particularly in a perivascular distribution. LAMMA studies noted t hat mineral deposits were primarily comprised of iron and aluminum. Th e severity of pathologic change correlated with the degree of clinical dysfunction. These studies demonstrate that, in contrast to Parkinson 's disease (PD) and MPTP-induced parkinsonism, manganese primarily dam ages the GP and SNr and relatively spares the nigrostriatal dopaminerg ic system. Further, the results suggest that Mn-induced parkinsonism c an be differentiated from PD and MPTP-induced parkinsonism by the clin ical syndrome and response to levodopa. The accumulation of iron and a luminum suggests that iron/aluminum-induced oxidant stress may contrib ute to the damage associated with Mn toxicity.