Velloso Nádia Aléssio, Dalmolin Gerusa Duarte, Fonini Graciela, Gindri Sinhorin Valéria Dornelles, Ferreira da Silveira Aron, Rubin Maribel Antonello, Mello Carlos Fernando
Department of Chemistry, Center of Exact and Natural Sciences, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
Brain Res. 2008 Mar 10;1198:107-14. doi: 10.1016/j.brainres.2007.12.056. Epub 2008 Jan 3.
Polyamines are aliphatic amines containing nucleophilic centers that are found in all eukaryotic cells, including brain cells. These compounds determine neuroprotection in experimental models of cerebral ischemia and neurotoxicity. In the current study we investigated the protective effects of spermine, an agonist of the polyamine binding site at the N-methyl-d-aspartate receptor, against the behavioral and neurochemical alterations induced by quinolinic acid. The unilateral intrastriatal injection of quinolinic acid (180 nmol/site into the dorsal striatum) induced stereotypical motor asymmetries, assessed by the open field and elevated body swing tests. Spermine modulated quinolinic acid-induced rotational behavior biphasically. While the previous intrastriatal administration of spermine at the dose of 0.1 nmol/site increased, the administration of spermine at the dose of 10 nmol/site reduced quinolinic acid-induced rotational behavior. Spermine (10 nmol/site) also decreased the contralateral swing behavior induced by quinolinic acid. Furthermore, the effect of 10 nmol of spermine was counteracted by the co-administration of arcaine (10 nmol), a selective antagonist of the polyamine binding site at the N-methyl-d-aspartate receptor. In addition, spermine (10 nmol) protected against quinolinic acid-induced protein carbonylation in the rat striatum, further suggesting an antioxidant role for this polyamine. These results provide evidence that the behavioral and biochemical alterations induced by quinolinic acid are attenuated or prevented by spermine through its interaction with N-methyl-d-aspartate receptor and/or its antioxidant function.
多胺是含有亲核中心的脂肪族胺，存在于包括脑细胞在内的所有真核细胞中。这些化合物在脑缺血和神经毒性的实验模型中决定神经保护作用。在本研究中，我们研究了精胺（N-甲基-D-天冬氨酸受体上多胺结合位点的激动剂）对喹啉酸诱导的行为和神经化学改变的保护作用。单侧纹状体内注射喹啉酸（180 nmol/部位，注入背侧纹状体）会诱发刻板运动不对称，通过旷场试验和抬高身体摆动试验进行评估。精胺对喹啉酸诱导的旋转行为具有双相调节作用。先前纹状体内注射0.1 nmol/部位的精胺会增加喹啉酸诱导的旋转行为，而注射10 nmol/部位的精胺则会减少这种行为。精胺（10 nmol/部位）还减少了喹啉酸诱导的对侧摆动行为。此外，10 nmol精胺的作用会被共注射阿卡因（10 nmol，N-甲基-D-天冬氨酸受体上多胺结合位点的选择性拮抗剂）所抵消。另外，精胺（10 nmol）可保护大鼠纹状体免受喹啉酸诱导的蛋白质羰基化，进一步表明这种多胺具有抗氧化作用。这些结果提供了证据，表明喹啉酸诱导的行为和生化改变可通过精胺与N-甲基-D-天冬氨酸受体的相互作用和/或其抗氧化功能而被减弱或预防。
