东莨菪碱慢性给药大鼠作为老龄相关记忆损害模型的探索

目的对东莨菪碱慢性给药大鼠能否作为老龄相关记忆损害模型进行探索。方法14只1月龄SD大鼠随机分为对照组和东莨菪碱模型组。东莨菪碱模型组大鼠皮下注射东莨菪碱2mg kg,2次日,正常对照组予等量生理盐水,连续21d。然后利用Morris水迷宫(MWM)参照记忆试验进行行为学测试;神经元的特殊染色及电子显微镜技术,观察大鼠海马CA1、CA3区锥体细胞数、超微结构的改变以及突触可塑性变化。结果东莨菪碱组大鼠隐匿平台搜索实验成绩有一定损害;两组大鼠空间探索次数差异无显著性(P>0.05)。两组间海马CA1、CA3区锥体细胞数差异无显著性(P>0.05)。两组大鼠锥体细胞胞体超微结构无差异,但两组大鼠CA1区神经元突触超微结构有轻微变化。结论东莨菪碱慢性给药对大鼠学习记忆能力有一定损害,但对长时记忆无明显影响;对海马神经元结构无明显损害,对神经元突触可塑性有轻微影响。此种动物模型可能不是理想的老年性痴呆或老年相关记忆损害模型。

Exploration on Animal Model for Senile Memory Deficits Induced by Repeatedly Giving Multiple Doses of Scopolamine to Rats

Objective To explore whether repeatedly administered multiple doses of scopolamine to rats is suitable for establishment of an animal model for senile memory deficits or Alzheimer disease research. Methods 14 rats were randomly divided into two groups (n=7): normal control group and scopolanmine treated group. In the experimental group, the rats received subcutaneous injection of scopolamine in a dose of 2mg/kg, twice a day for 21 consecutive days. The normal rats received the same volume of saline. Then reference memory testing in Morris water maze(MWM)was followed. Nissl staining was adopted to count the number of pyramidal cells in hippocampal CA1 and CA3 areas under light microscope. Ultrastructural changes of CA1 cells were examined by transmission electron microscopy. Results In the experimental group, escape latencies were statistically not significantly different from those of normal control rats on day 1, 2, 4 and 5, except day 3 in place navigation trials. In spatial probe trials, there were no significant differences between two groups. The quantity of pyramidal cells in hippocampal CA1 and CA3 areas was not significantly different between two groups. Ultrastructure of the pyramidal cells including nuclei and cytoplasmic organelles was not much changed. However, the neurons showed a decreased number of synaptic vesicles and reduced post synaptic density (PSD) in scopolamine treated rats in comparison with those of control rats. Conclusions Scopolamine given to rats in repeated doses may produce mild impairment of reference memory in Morris water maze. The number and ultrastructure of pyramidal neurons in CA1 and CA3 areas are not seriously changed, but some abnormalities of synapses in hippocampal CA1 cells may occur. Those findings indicate that scopolamine given in repeated doses to rats is not an ideal approach to establish an animal model for Alzheimer disease or senile memory deficits research.