Borlongan C V, Koutouzis T K, Randall T S, Freeman T B, Cahill D W, Sanberg P R
Department of Surgery, University of South Florida College of Medicine, Tampa 33612-4799, USA.
Brain Res Bull. 1995;36(6):549-56. doi: 10.1016/0361-9230(94)00242-s.
Previous animal studies have demonstrated that systemic administration of 3-nitropropionic acid (3-NP) leads to neuropathological changes similar to those seen in Huntington's disease (HD). Recently, we reported hypoactivity in 6- and 10-week old rats treated with systemic 3-NP (IP, 10 mg/kg/day) once every 4 days for 28 days. Although these behavioral results seem to differ from the observed hyperactivity in most excitotoxic models of HD, 3-NP may provide a better model of juvenile onset and advanced HD. In the present study, older rats were similarly treated with 3-NP to further characterize the reported age dependency of striatal neuronal death caused by 3-NP. Hypoactivity was observed in 14- and 28-week old rats with the latter demonstrating more profound features. The present study also provided the first direct evidence of a 3-NP effect on passive avoidance behavior. Experimental and control animals showed no significant difference in daytime acquisition and retention of a passive avoidance task. However, when the retention tests were conducted during the night time (in contrast to previous daytime tests), 3-NP-treated animals exhibited significant retention deficits. In addition, the neuropathological effects of 3-NP were determined by Nissl, AChE and NADPH-diaphorase histochemistry. Metabolic activity was studied using cytochrome oxidase activity as an index. Results revealed striatal glial infiltration, loss of intrinsic striatal cholinergic neurons, but some sparing of large AChE positive neurons, minimal damage of NADPH-diaphorase-containing neurons, and very slight, if any, alterations in cytochrome oxidase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
先前的动物研究表明，全身给予3-硝基丙酸（3-NP）会导致与亨廷顿舞蹈病（HD）相似的神经病理学变化。最近，我们报道了对6周龄和10周龄大鼠每4天腹腔注射一次3-NP（10mg/kg/天），持续28天，会导致其活动减少。尽管这些行为结果似乎与大多数HD兴奋性毒性模型中观察到的多动不同，但3-NP可能为青少年期和晚期HD提供了一个更好的模型。在本研究中，对老年大鼠同样给予3-NP处理，以进一步明确所报道的3-NP引起的纹状体神经元死亡的年龄依赖性。在14周龄和28周龄大鼠中观察到活动减少，后者表现出更明显的特征。本研究还首次直接证明了3-NP对被动回避行为的影响。实验动物和对照动物在被动回避任务的白天习得和保持方面没有显著差异。然而，当在夜间进行保持测试时（与之前的白天测试相反），经3-NP处理的动物表现出显著的保持缺陷。此外，通过尼氏染色、乙酰胆碱酯酶（AChE）和还原型辅酶Ⅱ-黄递酶（NADPH-d）组织化学方法确定3-NP的神经病理学效应。以细胞色素氧化酶活性为指标研究代谢活性。结果显示纹状体有胶质细胞浸润、内在纹状体胆碱能神经元丢失，但一些大的AChE阳性神经元保留，含NADPH-d的神经元损伤最小，细胞色素氧化酶活性即使有改变也非常轻微。（摘要截选至250字）
