2,2’,4,4’-四溴联苯醚染毒对大鼠学习记忆及海马NMDA受体亚基基因NR1和NR2B的影响

Effect of BDE-47 exposure on learning and the expression of genes memory and NR1 and NR2B of Hippocampal neurons in adult rat

目的:观察2,2’,4,4’-四溴联苯醚(2,2’,4,4’-tetrabromo-diphenyl ethers,BDE-47)染毒后大鼠学习记忆及海马NMDA受体亚基NR1和NR2B的变化,探讨BDE-47暴露对学习记忆的影响及其机制。方法:将80只SD雄性大鼠随机分为空白对照组、溶剂对照组、BDE-47(0.1 mg/Kg、0.5 mg/Kg和1.0 mg/Kg)剂量组,每组16只,每天灌胃1次,持续30 d;用Morris水迷宫检测学习记忆,用免疫组化检测大鼠NMDA受体亚基NR1和NR2B的表达,用RT-PCR检测大鼠NMDA受体亚基NR1和NR2B的基因表达。结果:在水迷宫试验中:与溶剂对照组比较,BDE-47染毒各组的平均逃避潜伏期明显增加、穿越平台的次数和在原平台象限停留的时间明显减少(P<0.05),且呈剂量-反应关系(P<0.05)。免疫组化结果:与溶剂对照组比较,各染毒组大鼠海马NMDA受体亚基NR1和NR2B表达明显减少(P<0.05),且呈剂量-反应关系(P<0.05)。RT-PCR结果与溶剂对照组比较,BDE-47染毒各组大鼠海马NMDA受体亚基NR1的基因表达明显减少(P<0.05);各染毒剂量组之间,随着染毒剂量的增加,大鼠海马NMDA受体亚基NR1和NR2B的基因表达减少(P<0.05)。结论:BDE-47染毒后大鼠学习记忆能力降低,可能与大鼠海马NMDA受体亚基NR1和NR2B减少有关。

Objiective： To study the effect and mechanism of 2, 2＇, 4, 4＇-tetrabromo-diphenyl ethers （BDE-47） exposure on spatial learning and memory abilities and the genes expression of NMDA-receptor subunit in adult rats. Methods： 80 healthy male SD rats were randomly divided into control group,vehicle group and three BDE-47-treated groups. The latter3 treated groups were treated by intragastric administration of 0.1 mg/kg, 0.5 mg/kg and 1.0 mg/kg BDE-47 once a day respectively. The rats in vechicle group received 1.0 mg/kg of peanut oil.The administration was lasted for 30 days. After experiment the capability of learning and memory of rats were measured by Morris water maze test. The expressions of both subunits of NMDA-receptor were evaluated by immunohistochemisty. Results： In BDE-47-treated groups the average escape latency was increased compared with control group （P〈 0.05）, and the freguency the animal crossed the original platform and the time spent in quadrant of the original platform were decreased compared with control group and dosage related （P〈 0.05）. The expression of NR1 and NR2B in CA1, CA3 and dentate gyrus areas of hippocampus were significantly decreased in the BDE-47 treated groups compared with the vehicle group and dosage related （P〈0.05）.And the expression mRNA of NR1 and NR2B showed statistically signifcant decrease in rats exposed to BDE-47. Conclusions：These findings show that the exposure to BDE-47 can induce behavioral alterations which may be due to the down-regulation of the genes expression of subunits of NMDA receptors.