The regional distribution of monoamine oxidase activities towards different substrates: effects in rat brain of chronic administration of manganese chloride and of ageing.

Abstract

The effects of chronic manganese chloride administration (1 mg MnCl2.4H2O/ml of drinking water) and ageing on the regional distribution of monoamine oxidase (MAO, EC 1.4.3.4) were studied in 2-month- and 24-28-month-old rats. In both the control and Mn-treated rats, the serotonin oxidation (type A) rates decreased in hypothalamus, pons and medulla, striatum, midbrain and cerebral cortex, but not in cerebellum, in ageing. On the other hand the benzylamine oxidation (type B) rates in hypothalamus, striatum and cerebral cortex increased in ageing. In all regions except the cerebellum, there was a uniform decrease in the A/B ratio. This decrease was verified by differential inhibition studies using clorgyline and L-deprenyl, specific type A and type B inhibitors respectively. The dopamine-oxidising rates decreased in all regions, except the cerebral cortex and the cerebellum, in ageing control rats. This age-related decrease was not seen in the striatum and midbrain of manganese-treated rats. In these rats the other effect was an age-related increase in the rate of oxidation of all the amines in the cerebellum, not observed in control rats. These selective effects of manganese are only seen when comparing age-related changes in both groups of animals, since comparison of manganese-treated rats with age-matched controls showed a significant difference only in the rate of serotonin oxidation in the cerebellum of 2-month-old rats. The relationship of these observations to the effects of ageing and manganese encephalopathy on specific amine systems is discussed.