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- Title
QUINOLINIC ACID MILDLY IMPAIRS CEREBRAL ENERGY METABOLISM.
- Authors
Schuck, Patrícia F.; Ferreira, Gustavo C.; Tonin, Anelise; Ceolato, Paula C.; Wajner, Moacir
- Abstract
Quinolinic acid (QA) is found at increased concentrations in brain of patients affected by various neurodegenerative disorders, including Huntington's and Alzheimer's diseases. Considering that the neuropathology of these disorders has been recently attributed at least in part to energy deficit, we investigated the in vitro effect of QA on various parameters of cerebral energy metabolism. We observed that QA increased glucose uptake, whereas 14CO2 generation from glucose, acetate and citrate was inhibited. Furthermore, QA-induced increase of glucose uptake was prevented by the NMDA receptor antagonist MK-801. Complex II activity was also inhibited by QA, and this inhibition was prevented by pre-incubating homogenates with catalase plus superoxide dismutase, indicating that this effect was probably mediated by reactive oxygen species. In addition, the activity of lactate dehydrogenase was decreased by QA. The other activities of the respiratory chain complexes, Krebs' cycle enzymes, creatine kinase and Na+,K+-ATPase and lactate production were not affected by the acid. QA did not change the oxygen consumption in the presence of glutamate/malate or succinate as well, suggesting that its effect on cellular respiration was rather weak. The data provide evidence that QA provokes a mild impairment of cerebral energy metabolism and does not support the view that the brain energy deficiency associated to neurodegenerative disorders could be solely endorsed to QA accumulation.
- Subjects
QUINOLINIC acid
- Publication
Neurotoxicity Research, 2008, Vol 13, Issue 2, p143
- ISSN
1029-8428
- Publication type
Abstract