Effect of subchronic aluminum exposure on learning and memory and c-Fos expression in CA1 area of hippocampus in Wistar rats / 中国药理学与毒理学杂志

ABSTRACT

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 and 8.0 g?L-1 AlCl3 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 hippo?campus in offspring rats were detected by RT-PCR and immunohistochemistry. RESULTS Learning and memory of offspring rats in AlCl3 groups were significantly lower than those in control group(P<0.01,P<0.05). The hippocampal Al concentrations of offspring rats in AlCl3 groups were higher than those in control group(P<0.01). The morphology in CA1 area of offspring rats′ hippocampus in AlCl3 groups exhibited sparse nerve fibers, depigmentation and even vacuolar degeneration in neurons and other pathological changes after Al treatment;c-fos mRNA expression in the hippocampus in 4.0 and 8.0 g?L-1 AlCl3 group rats was significantly lower than in control and 2.0 g?L-1 AlCl3 group, respectively(P<0.01). c-Fos protein expression in offspring rats′ hippocampus in AlCl3 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.