Neurochemical Research

, Volume 22, Issue 12, pp 1443–1447

Manganese Decreases Glutamate Uptake in Cultured Astrocytes

  • Alan S. Hazell
  • Michael D. Norenberg
Article

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.

Manganese glutamate transport ammonia hepatic encephalopathy astrocyte 

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Copyright information

© Plenum Publishing Corporation 1997

Authors and Affiliations

  • Alan S. Hazell
    • 1
    • 2
  • Michael D. Norenberg
    • 1
    • 2
    • 3
  1. 1.Laboratory of NeuropathologyVeterans Administration Medical CenterMiami
  2. 2.Department of PathologyUniversity of Miami School of MedicineMiami
  3. 3.Department of Biochemistry & Molecular BiologyUniversity of Miami School of MedicineMiami

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