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Manganese Decreases Glutamate Uptake in Cultured Astrocytes

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Abstract

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 μM 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 Vmax, with no change in the Km. Treatment of cultures with 5 mM NH4Cl inhibited D-aspartate uptake by 21%, and a combination of 5 mM NH4Cl with 100 μM manganese produced an additive effect on uptake inhibition. These results suggest a pathogenetic role for manganese in HE, possibly involving glutamate transport.

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Authors and Affiliations

  1. Laboratory of Neuropathology, Veterans Administration Medical Center, Miami, Florida, 33125

    Alan S. Hazell & Michael D. Norenberg

  2. Department of Pathology, University of Miami School of Medicine, Miami, Florida, 33101

    Alan S. Hazell & Michael D. Norenberg

  3. Department of Biochemistry & Molecular Biology, University of Miami School of Medicine, Miami, Florida, 33101

    Michael D. Norenberg

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Hazell, A.S., Norenberg, M.D. Manganese Decreases Glutamate Uptake in Cultured Astrocytes. Neurochem Res 22, 1443–1447 (1997). https://doi.org/10.1023/A:1021994126329

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