生命早期暴露于百草枯和代森锰对子代SD大鼠认知记忆功能的影响

doi:10.3969/j.issn.1004-616x.2016.03.012

癌变·畸变·突变 ›› 2016, Vol. 28 ›› Issue (3): 218-222,226.doi: 10.3969/j.issn.1004-616x.2016.03.012

生命早期暴露于百草枯和代森锰对子代SD大鼠认知记忆功能的影响

李柏, 孙艳, 李百祥

哈尔滨医科大学公共卫生学院卫生毒理学教研室, 黑龙江哈尔滨 150081

收稿日期:2016-02-29 修回日期:2016-04-25 出版日期:2016-05-31 发布日期:2016-05-31
通讯作者: 李百祥,E-mail:libaix@ems.hrbmu.edu.cn;孙艳,E-mail:13946167049@163.com E-mail:libaix@ems.hrbmu.edu.cn;13946167049@163.com
作者简介:李柏,E-mail:hmuleetina@163.com。
基金资助:
国家自然科学基金(青年科学基金)资助项目(81402711)

Exposure of Sprague Dawley rat pups to paraquat and maned affected their cognition and memory

LI Bai, SUN Yan, LI Baixiang

Department of Toxicology, College of Public Health, Harbin Medical University, Harbin 150081, Heilongjiang, China

Received:2016-02-29 Revised:2016-04-25 Online:2016-05-31 Published:2016-05-31

摘要/Abstract

摘要： 目的:探讨生命早期联合暴露于农业除草剂百草枯(PQ)和杀真菌剂代森锰(MB)对子代大鼠海马内认知及记忆功能相关基因表达的影响及可能机制。方法:清洁级SD大鼠随机分为3组,即对照组(生理盐水)和低(PQ 10 mg/kg+MB 30 mg/kg)、高(PQ 15 mg/kg+MB 45 mg/kg)剂量染毒组,孕第5天起经口染毒直至仔鼠出生后21 d断乳。仔鼠继续饲养(未染毒)至3月龄,进行Morris水迷宫实验,比较其穿梭次数。取仔鼠海马组织对其形态变化进行光镜和透射电镜观察,并通过实时荧光定量PCR(qPCR)和蛋白免疫印迹技术(Western blot)分别检测海马环磷腺苷效应元件结合蛋白(CREB)、磷酸化的环磷腺苷效应元件结合蛋白(P-CREB)及脑源性神经营养因子(BDNF)mRNA和蛋白表达量的变化。结果:与对照组相比,Morris水迷宫结果显示,染毒剂量组仔鼠运动轨迹明显复杂,且穿梭次数显著减少,差异具有统计学意义(P<0.05);光镜下高剂量染毒组海马细胞形态变化明显;电镜下各染毒剂量组海马神经元超微结构均出现明显变化;qPCR结果显示,各染毒剂量组仔鼠CREB、P-CREB和BDNF mRNA表达量显著下降,差异具有统计学意义(P<0.05,低剂量组BDNF mRNA除外)。蛋白免疫印迹结果显示,各染毒剂量组仔鼠海马中CREB、P-CREB和BDNF蛋白表达显著降低,差异具有统计学意义(P<0.05,低剂量染毒组CREB蛋白除外)。结论:生命早期联合暴露于PQ和MB可能通过影响仔鼠海马内认知及记忆功能相关基因表达,造成子代大鼠认知及记忆功能的损伤。

关键词: 生命早期, 百草枯, 子代大鼠, 行为, 认知, 记忆

Abstract: OBJECTIVE:We evaluated the combined effects of paraquat and maneb on expression of cognition- and memory-related genes in hippocampus of Sprague Dawley pups. METHODS:Pregnant SD rats were randomly divided into three groups:control (physiological saline) and PQ-MB treatment (PQ 10 mg/kg+MB 30 mg/kg and PQ 15 mg/kg +MB 45 mg/kg). They were treated twice a week with PQ-MB from day 5 after pregnancy till ablactation. Pups at 3-month old and their tissues were evaluated using Morris water maze, optical microscopy, electron microscopy, fluorescence PCR and Western blot for changes in behavior, morphology of hippocampus, microstructure of hippocampal neurons, mRNA and protein levels of CREB, P-CREB and BDNF. We use ANOVA to analyze the experimental data. RESULTS:Morris water maze showed that the exposed groups had obvious complex trajectories and a significantly reduced number of shuttle (P<0.05) compared to the control group. Both optical and electron microscopic investigations showed obvious morphological changes in hippocampus of high-dose exposed pups. There was a significant reduction in mRNA expressions among all the treated groups (P<0.05) and significant decrease in hippocampus CREB, P-CREB and BDNF protein levels(P<0.05). CONCLUSION:Combined exposure to paraquat and maneb in utero may impact cognition and memory of Sprague Dawley rat pups via down-regulating the expression of related genes in hippocampus.

Key words: early life, paraquat, pups, behavior, cognition, memory

中图分类号:

R114

李柏, 孙艳, 李百祥. 生命早期暴露于百草枯和代森锰对子代SD大鼠认知记忆功能的影响[J]. 癌变·畸变·突变, 2016, 28(3): 218-222,226.

LI Bai, SUN Yan, LI Baixiang. Exposure of Sprague Dawley rat pups to paraquat and maned affected their cognition and memory[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2016, 28(3): 218-222,226.

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生命早期暴露于百草枯和代森锰对子代SD大鼠认知记忆功能的影响

Exposure of Sprague Dawley rat pups to paraquat and maned affected their cognition and memory

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