Quinolinic acid neurotoxicity: in vivo increased copper and manganese content in rat corpus striatum after quinolinate intrastriatal injection.
Copper and manganese, two essential metals involved in physiological and physiopathological processes in the brain, were measured in corpora striata of rats 7 days after intrastriatal injection of quinolinic acid (QUIN, 240 nmol/l microliters), an N-methyl-D-aspartate (NMDA) receptor agonist with toxic activity. Seven days after QUIN administration, copper and manganese contents were assessed by graphite furnace atomic absorption spectrophotometry. Total copper content was increased by 152% in QUIN-treated rats (18.74 +/- 2.05 micrograms/g) as compared to control animals (7.44 +/- 1.15 micrograms/g), whereas manganese striatal levels were enhanced by 35% (0.30 +/- 0.02 microgram/g) vs. control values (0.22 +/- 0.02 microgram/g). Quinolinate-induced striatal increase in copper and manganese levels were prevented by 23% (9.18 +/- 1.43 micrograms/g) and -0.45% (0.22 +/- 0.03 microgram/g) vs. control values, respectively, in rats pretreated with an NMDA receptor antagonist, dizocilpine (MK-801, 10 mg/kg, i.p.), 60 min before QUIN administration. As an index of QUIN neurotoxicity, striatal GABA levels were also measured 7 days after QUIN injection. GABA content was decreased by-55% in QUIN-lesioned rats (96.37 +/- 8.92 micrograms/g), whereas MK-801 was able to block QUIN-induced GABA depletion by 2% (219.37 +/- 10.60) vs. control values (214.2 +/- 21.88 micrograms/g). These findings suggest that increased concentrations of transition metals can be mediated by selective overactivation of NMDA receptors and might be a consequence of neural loss as well as glial response to damage.
Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, S.S., Mexico.
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Santamaría
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Ríos
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Pérez
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Flores
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Galván-Arzate
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Osorio-Rico
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Solís
D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000378:metabolism*; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008345:Manganese / Q000378:metabolism*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology; D017378:Quinolinic Acid / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000037:antagonists & inhibitors; D013054:Spectrophotometry, Atomic; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D008345:Manganese; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate; D003300:Copper; D017378:Quinolinic Acid