Pérez P, Flores A, Santamaría A, Ríos C, Galván-Arzate S
Departamento de Neuroquimica, Instituto Nacional de Neurología y Neurología, Manuel Velasco Suárez, S.S., México, D.F.
Arch Med Res. 1996 Winter;27(4):449-52.
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.
在单侧纹状体注射喹啉酸（QUIN，240 nmol/1微升）——一种内源性N-甲基-D-天冬氨酸（NMDA）受体激动剂——7天后，测量了五只大鼠脑内五个区域的总铜和锰含量。使用石墨炉原子吸收分光光度法评估了盐水处理组和QUIN处理组大鼠脑皮质、海马体、纹状体、中脑和小脑组织中这两种过渡金属的浓度。纹状体注射QUIN后，在小脑、海马体、中脑和纹状体中观察到铜含量增加（分别比对照值增加37%、55%、71%和152%），但脑皮质中未增加。仅在QUIN处理组大鼠的纹状体中发现锰水平比对照值提高了35%，而在所有其他分析的脑区域中未发现。在用NMDA受体拮抗剂地佐环平（MK-801，10 mg/kg，腹腔注射）预处理大鼠60分钟后再进行QUIN微量注射，可部分阻止QUIN诱导的海马体、中脑和纹状体区域铜含量增加（分别比对照增加17%、57%和23%）。地佐环平对QUIN诱导的纹状体锰含量增加也有相同的保护作用（比对照减少0.45%）。这些发现与在亨廷顿舞蹈病死后大脑中观察到的变化相似，表明铜而非锰的区域含量改变可能是QUIN诱导的神经毒性事件通过QUIN对NMDA受体的作用扩散到纹状体组织至大脑邻近区域的结果。
