Velloso Nádia A, Dalmolin Gerusa D, Gomes Guilherme M, Rubin Maribel A, Canas Paula M, Cunha Rodrigo A, Mello Carlos F
Department of Chemistry, Center of Exact and Natural Sciences, Universidade Federal de Santa Maria, Santa Maria 97105-900, RS, Brazil.
Neurobiol Learn Mem. 2009 Nov;92(4):574-80. doi: 10.1016/j.nlm.2009.07.006. Epub 2009 Jul 24.
Huntington's disease (HD) is a progressive neurodegenerative disorder associated with motor and cognitive impairment. Intrastriatal administration of quinolinic acid (QA) causes neurodegeneration, glial proliferation and cognitive impairment in animals, which are similar to these seen in human HD. Since polyamines improve memory in cognitive tasks, we now tested if the post-training intrastriatal administration of spermine, an agonist of the polyamine site at the NMDA receptor, reverses the deficits in the object recognition task induced by QA. Bilateral striatal injections of QA (180 or 360 nmol/site) caused object recognition impairment, neuronal death and reactive astrogliosis. A single injection of spermine (0.1 and 1 nmol/site), 5 days after QA injection, reversed QA-induced impairment of object recognition task. Spermine (0.1 nmol/site) also inhibited QA-induced reactive astrogliosis measured by a semi-quantitative determination of GFAP immunolabelling, but did not alter neuronal death, measured by a semi-quantitative determination of fluoro-Jade C staining. These results suggest that polyamine binding sites may be considered a novel therapeutic target to prevent reactive astrogliosis and mnemonic deficits in HD.
亨廷顿舞蹈症（HD）是一种与运动和认知障碍相关的进行性神经退行性疾病。纹状体内注射喹啉酸（QA）会导致动物出现神经退行性变、胶质细胞增生和认知障碍，这些症状与人类HD患者所见相似。由于多胺可改善认知任务中的记忆，我们现在测试了在训练后纹状体内注射精胺（NMDA受体多胺位点的激动剂）是否能逆转QA诱导的物体识别任务缺陷。双侧纹状体注射QA（180或360 nmol/部位）导致物体识别障碍、神经元死亡和反应性星形胶质细胞增生。在QA注射5天后单次注射精胺（0.1和1 nmol/部位）可逆转QA诱导的物体识别任务损伤。精胺（0.1 nmol/部位）还通过对GFAP免疫标记的半定量测定抑制了QA诱导的反应性星形胶质细胞增生，但通过对氟玉红C染色的半定量测定未改变神经元死亡情况。这些结果表明，多胺结合位点可能被视为预防HD中反应性星形胶质细胞增生和记忆缺陷的新治疗靶点。
