Differences in the Neurotoxic Effects of Manganese During Development and Aging: Some Observations on Brain Regional Neurotransmitter and Non-neurotransmitter Metabolism in a Developmental Rat Model of Chronic Manganese Encephalopathy

The effects of chronic and life-span (i.e. over 2 years) treatment with manganese (1 mg MnCl2.4H2O per ml of drinking water) on a number of neurochemical parameters were studied. In development Mn-treatment led to transient but age-dependent decreases in synaptosomal dopamine uptake in hypothalamus, striatum and mid-brain and decreases in synaptosomal choline uptake in hypothalamus but increase in synaptosomal choline uptake in striatum. However, synaptosomal noradrenaline and serotonin uptake in these brain regions remained unaltered. Mn-treatment in development led to small decreases in choline acetyltransferase activities in cerebellum and mid-brain of 2 month old rats but did not affect the regional distribution of glutamic acid decarboxylase or acetylcholinesterase. The same treatment did not alter regional distribution of NAD-linked isocitric dehydrogenase although treatment with a high dose (10 mg MnCl2.4H2O per ml) resulted in transient but age-dependent decreases in the activities of this enzyme but not those of glucose-6-phosphate dehydrogenase in cerebral cortex and mid-brain. Lifespan Mn-treatment (1 mg MnCl2.4H2O per ml) exerted antagonistic effects on the age-related changes in activities of several enzymes. These results suggest that chronic Mn toxicity selectively affects several neurochemical paradigms and the long-term effects of Mn toxicity on brain development and aging are different.