Brain regional manganese distribution after chronic manganese treatment

Chronic manganese encephalopathy in man is characterized by an initial, and more acute, phase of psychosis, followed by disturbances of the extra-pyramidal system not unlike those of Parkinson's disease (Cotzias et al., 1971). Little information is presently available regarding the concentrations of manganese in different brain regions during the pathogenesis of this disease, although there is some suggestion that the regional distribution of this and other transition metals in the human brain is by no means uniform (Curzon, 1975). The distribution of some trace metals in rat and rabbit brain (Hanig & Aprison, 1967; Donaldson et al., 1973) is consistent with this notion. Since we have observed region-specific changes in a number of neurochemical markers in the developmental rat model of chronic manganese encephalopathy (J. Lai, T. Leung & L. Lim, unpublished work), the brain regional distribution of manganese in this animal model has been studied using the sensitive and specific technique of neutron activation analysis. Wistar rats (M.R.C. Porton strain) were administered manganese (MnC1,,4H20, lmg/ml of tap water) via their drinking water at mating. After 10-14 days the males were separated from the pregnant females. Within 48 h of birth the litter size was adjusted to 8-10 pups. Litters were weaned at day 20/21 and the same drinking regimen was continued till the animals were used for experiments. Adult 130 day-old female rats were decapitated and their brains were dissected rapidly on a petri dish on ice by the procedure of Glowinski & Iversen (1 966) into seven regions: hypothalamus, cerebellum, pons and medulla, striatum, midbrain, cerebral cortex and hippocampus (Table 1). Each brain region was freeze-dried and its content of manganese was determined by neutron activation analysis (see Chan et af., 1981). Analysis of the significance of difference was performed using the non-paired t test. In the female rat brain, the manganese concentrations were highest in the midbrain and lowest in the hippocampus and cerebral cortex (Table 1). The manganese concentrations in the other four regions were similar (Table 1). Essentially the same results were also obtained when the concentrations were expressed in terms of per g dry weight of tissue (results not shown). Our results are similar to those reported by Hanig & Aprison (1967) for the rabbit but contrast with those of Donaldson et af . (1973) for the male rat. It is relevant that both groups of workers (Hanig & Aprison, 1967; Donaldson et al., 1973) employed complex procedures for sample preparation