Résumé
Total copper and manganese contents were measured in five rat brain regions 7 days after a unilateral striatal injection of quinolinic acid (QUIN, 240 nmol/1µl), an endogenous N-methyl-D-aspartate (NMDA) receptor agonist. Concentrations of both transition metals were evaluated in tissue of brain cortex, hippocampus, corpus striatum, midbrain and cerebellum of saline- and QUIN-treated rats using graphite furnace atomic absorption spectrophotometry. Increases in copper content were observad after QUIN striatal injection in cerebellum, hippocampus, midbrain and corpus striatum (37, 55, 71 and 152 percent as compared against control values, respectively) but not in brain cortex. Manganese levels were found enhanced only in corpus striatum of QUIN-treated rats by 35 percent vs. control values, but not in all other brain regions analyzed. QUIN-induced increases in regional copper content were partially prevented in hippocampus, midbrain and striatum (17, 57, and 23 percent vs. control, respectively) by pretreatment of rats with an NMDA receptor antagonist, dizocilpine (MK-801, 10 mg/kg, i.p.), administered 60 min before QUIN microinjection. The same protective effect of fizocilpine was observed against QUIN-induced enhancement of striatal manganese content (-0.45 percent vs. control). These findings resemble those changes observed in postmortem Huntington's disease brain and suggest that alterations in regional content of copper, but not in manganese, may be a consequence of the spreading of QUIN-induced neurotoxic events into the striatal tissue to the neighboring regions of the brain, by action of QUIN on NMDA receptors