亚慢性铝暴露对Wistar大鼠学习记忆及海马CA1区c-Fos表达的影响

Effect of subchronic aluminum exposure on learning and memory and c-Fos expression in CA1 area of hippocampus in Wistar rats

目的探讨亚慢性铝暴露对大鼠学习记忆能力和c-Fos表达的影响,探索铝对大鼠认知功能损害的毒性作用及机制。方法 Wistar子代大鼠自出生之日起,分别通过乳汁或饮水染毒Al Cl32.0,4.0和8.0 g?L^(-1)连续3个月。Morris水迷宫法检测子代大鼠的学习记忆能力,石墨炉原子吸收光谱法检测子代大鼠海马铝含量,HE染色观察海马CA1区神经细胞形态,RT-PCR法检测子代大鼠海马CA1区c-fos基因表达,免疫组化法检测CA1区c-Fos蛋白表达。结果染Al Cl3组子代大鼠学习记忆能力明显低于对照组(P<0.05,P<0.01),海马的铝含量高于对照组(P<0.01),其海马CA1区神经细胞呈现神经纤维稀疏、神经元细胞脱失甚至空泡样变性等病理改变;染Al Cl34.0和8.0 g?L^(-1)组子代大鼠海马c-fos m RNA表达水平分别低于对照组和染Al Cl32.0 g?L^(-1)组(P<0.01)。染Al Cl3组子代大鼠CA1区c-Fos蛋白表达水平低于对照组(P<0.01)。结论亚慢性铝暴露损害大鼠学习记忆能力的机制可能与Al Cl3造成海马CA1区神经细胞病理学改变、功能减弱以及c-Fos表达水平降低有关。

OBJECTIVE To study the effect of subchronic exposure to aluminum（Al）on learning,memory,and immediate early gene expression in rats,and to explore the toxic mechanism of Al on cognitive impairment of rats. METHODS Wistar offspring rats were administered with 2.0,4.0 and8.0 g·L-1Al Cl3 in milk and drinking water in sequence from the postnatal day 1 to 3 months. Then,learning and memory of offspring rats were measured by Morris water maze, the hippocampal Al concentration was quantitated by the atomic absorption spectrophotometer, the CA1 area of the hippocampus was collected for HE observation, and the c-fos gene and c-Fos protein expression in CA1 area of the hippocampus in offspring rats were detected by RT- PCR and immunohistochemistry. RESULTS Learning and memory of offspring rats in Al Cl3 groups were significantly lower than those in control group（P〈0.01,P〈0.05）. The hippocampal Al concentrations of offspring rats in Al Cl3 groups were higher than those in control group（P〈0.01）. The morphology in CA1 area of offspring rats′ hippocampus in Al Cl3 groups exhibited sparse nerve fibers, depigmentation and even vacuolar degeneration in neurons and other pathological changes after Al treatment;c-fos m RNA expression in the hippocampus in 4.0 and8.0 g·L^- 1Al Cl3 group rats was significantly lower than in control and 2.0 g·L^- 1Al Cl3 group,respectively（P〈0.01）. c-Fos protein expression in offspring rats′ hippocampus in Al Cl3 exposed groups was significantly lower compared with control group（P〈0.01）. CONCLUSION Al can injure learning and memory of rats,which is related to hippocampal neuronal dysfunction in CA1 area induced by pathological changes,low levels of c-fos gene and c-Fos protein expression subsequently.