Department of Physiology, Science and Research Branch, Islamic Azad University, Fars, Iran.
Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
Cell J. 2014 Fall;16(3):325-34. Epub 2014 Oct 4.
The cerebellum is a key structure involved in coordinated motor planning, cognition, learning and memory functions. This study presents a permanent model of a toxin produced cerebellar lesion characterized according to contemporary motor and cognitive abnormalities.
In this experimental study, slow administration of quinolinic acid (QA, 5 µl of 200 µmol, 1 µl/minute) in the right cerebellar hemisphere (lobule VI) caused noticeable motor and cognitive disturbances along with cellular degeneration in all treated animals. We assessed behavioral and histopathological studies over ten weeks after QA treatment. The data were analyzed with ANOVA and the student's t test.
The QA treated group showed marked motor learning deficits on the rotating rod test (p=0.0001), locomotor asymmetry on the cylinder test (p=0.0001), dysmetria on the beam balance test (p=0.0001), abnormalities in neuromuscular strength on the hang wire test (p=0.0001), spatial memory deficits in the Morris water maze (MWM, p=0.001) and fear conditioned memory on the passive avoidance test (p=0.01) over a ten-week period compared with the control animals. Histopathological analysis showed loss of Purkinje cells (p=0.001) and granular cell density (p=0.0001) in the lesioned hemisphere of the cerebellum.
Results of the present study show that QA can remove numerous cells which respond to this toxin in hemispheric lobule VI and thus provide a potential model for functional and cell-based studies.
小脑是参与协调运动规划、认知、学习和记忆功能的关键结构。本研究提出了一种新的、永久性的毒素诱导小脑损伤模型，该模型具有当代运动和认知异常特征。
在这项实验研究中，缓慢向右侧小脑半球（VI 叶）内注射喹啉酸（QA，5μl，200μmol，1μl/min）导致所有接受治疗的动物都出现明显的运动和认知障碍以及细胞变性。我们在 QA 处理后 10 周进行行为和组织病理学研究。使用方差分析和学生 t 检验对数据进行分析。
QA 处理组在旋转棒测试中表现出明显的运动学习缺陷（p=0.0001），在圆筒测试中表现出运动不对称（p=0.0001），在平衡木测试中表现出运动失调（p=0.0001），在悬线测试中表现出神经肌肉力量异常（p=0.0001），在 Morris 水迷宫（MWM）测试中表现出空间记忆缺陷（p=0.001），在被动回避测试中表现出恐惧条件记忆异常（p=0.01），与对照组相比，这些异常在 10 周内持续存在。组织病理学分析显示，损伤半球的小脑浦肯野细胞（p=0.001）和颗粒细胞密度（p=0.0001）丧失。
本研究结果表明，QA 可以去除对这种毒素有反应的大量细胞，从而为功能和基于细胞的研究提供了一个潜在的模型。
