Role of manganese accumulation in increased brain glutamine of the cirrhotic rat

Neurochem Res. 2003 Jun;28(6):911-7. doi: 10.1023/a:1023279527545.


Cirrhosis promotes increases of both manganese and glutamine in brain. Manganese is a modulator and glutamine is the product of glutamine synthetase. This work studies the relationship between manganese and glutamine synthetase in a model of cirrhosis in the rat. We administered manganese (1 g/L) in the drinking water of sham-operated and bile-duct obstructed rats. We evaluated the manganese and glutamine accumulation and the glutamine synthetase activity in frontal cortex, striatum, and pallidum after 2, 4, and 6 weeks of biliary obstruction or sham surgery. Cirrhotic rats receiving manganese increased their brain content of metal about 400%-600% after 4 weeks of treatment (P < .05) and also remarkably accumulated glutamine through time in the three regions studied (P < .05 at week 6). Interestingly, bile-duct obstructed rats treated with manganese showed no effect on glutamine synthetase activity. Results from this study suggest that manganese induces increases of brain glutamine independently of its synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism*
  • Disease Models, Animal
  • Glutamate-Ammonia Ligase / metabolism
  • Glutamine / metabolism*
  • Kinetics
  • Liver Cirrhosis, Experimental / metabolism*
  • Male
  • Manganese / metabolism*
  • Organ Specificity
  • Rats
  • Rats, Wistar
  • Time Factors


  • Glutamine
  • Manganese
  • Glutamate-Ammonia Ligase