title: 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.
abstract: 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.
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000375:Aging; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002794:Choline / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D020149:Manganese Poisoning; D009243:NAD / Q000378:metabolism; D009422:Nervous System Diseases / Q000139:chemically induced*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects
chemical_list: D018377:Neurotransmitter Agents; D009243:NAD; D007521:Isocitrate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D000110:Acetylcholinesterase; D002794:Choline