Changes in transition metal contents in rat brain regions after in vivo quinolinate intrastriatal administration.
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/ 1 microliter), 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 observed after QUIN striatal injection in cerebellum, hippocampus, midbrain and corpus striatum (37, 55, 71 and 152% 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% 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% 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 dizocilpine was observed against QUIN-induced enhancement of striatal manganese content (-0.45% vs. control). These findings resemble those changes observed in postmortem Huntington's disease brains 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.
Pérez
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Departamento de Neuroquimica, Instituto Nacional de Neurología y Neurología, Manuel Velasco Suárez, S.S., México, D.F.
Flores
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Santamaría
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A
Ríos
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C
Galván-Arzate
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S
D000818:Animals; D002531:Cerebellum / Q000737:chemistry / Q000378:metabolism*; D003300:Copper / Q000032:analysis / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008345:Manganese / Q000032:analysis / Q000378:metabolism; D008636:Mesencephalon / Q000737:chemistry / Q000378:metabolism*; D008670:Metals / Q000032:analysis / Q000378:metabolism*; D017378:Quinolinic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013687:Telencephalon / Q000737:chemistry / Q000378:metabolism*
D008670:Metals; D008345:Manganese; D016291:Dizocilpine Maleate; D003300:Copper; D017378:Quinolinic Acid