Manganese decreases glutamate uptake in cultured astrocytes

Recent data have shown an accumulation of manganese in the basal ganglia in patients With chronic hepatic encephalopathy (HE). Astrocytes and ammonia are critically involved in the pathogenesis of HE, and we have recently demonstrated that ammonia decreases glutamate uptake in cultured astrocytes. Since failure by astrocytes to take up glutamate may represent an important pathogenetic mechanism in HE, we, therefore, examined the effect of manganese on glutamate transport in these cells. Treatment of cultured astrocytes with 100 mu M manganese for 2 days resulted in a 54% decrease in the uptake of D-aspartate, a nonmetabolizable analogue of glutamate. Kinetic analysis revealed a 28% decline in V-max, with no change in the K-m. Treatment of cultures with 5 mM NH4 Cl inhibited D-aspartate uptake by 21%, and a combination of 5 mM NH4Cl with 100 mu M manganese produced an additive effect on uptake inhibition. These results suggest a pathogenetic role for manganese in HE, possibly involving glutamate transport.