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新生期暴露于内分泌干扰化学物质会通过破坏雄性瑞士白化小鼠的海马结构来损害学习行为。

Neonatal Exposure to Endocrine Disrupting Chemicals Impairs Learning Behaviour by Disrupting Hippocampal Organization in Male Swiss Albino Mice.

作者信息

Bhaskar Rakesh, Mishra Ashish K, Mohanty Banalata

机构信息

Department of Zoology, University of Allahabad, Allahabad, India.

出版信息

Basic Clin Pharmacol Toxicol. 2017 Jul;121(1):44-52. doi: 10.1111/bcpt.12767. Epub 2017 Mar 15.

Abstract

Hippocampus is highly susceptible to endocrine disrupting chemicals exposure particularly during the critical phase of brain development. In this study, mice offspring were exposed to endocrine disruptors mancozeb (MCZ) and imidacloprid (IMI) individually (40 mg MCZ and 0.65 mg IMI/kg/day) as well as to their equimixture (40 mg MCZ + 0.65 mg IMI/kg/day) through the diet of lactating mothers from post-natal day (PND) 1 to PND 28. Half of the randomly selected male offspring were killed at PND 29, and the rest half were left unexposed and killed at PND 63. Brain weight, histology, plasma hormone profile and working memory performance were the various end-points studied. Brain weight was significantly decreased in the mixture-exposed group at PND 29, which persisted to PND 63. Total thickness of pyramidal cell layers decreased significantly along with misalignment, shrinkage and degeneration of pyramidal neurons in CA1 and CA3 regions of the IMI and mixture-exposed groups. The length and branch points of dendrites of pyramidal neurons were decreased significantly in mixture-exposed group at both PND 29 and PND 63. Dendritic spine density was also reduced in mixture-exposed group offspring. Testosterone level was significantly decreased only at PND 29, but corticosterone level was increased at both PND 29 and PND 63 in mixture-exposed offspring. T-maze task performance revealed significantly increased time duration and reduced path efficiency in mixture-exposed group offspring. The results thus indicate that pesticide mixture exposure could lead to changes in learning behaviour even at doses that individually did not induce any adverse effect on hippocampal organization.

摘要

海马体极易受到内分泌干扰化学物质的影响,尤其是在大脑发育的关键阶段。在本研究中,小鼠后代从出生后第1天(PND1)到第28天,通过哺乳期母亲的饮食分别接触内分泌干扰物代森锰锌(MCZ)和吡虫啉(IMI)(40毫克MCZ和0.65毫克IMI/千克/天)以及它们的等比例混合物(40毫克MCZ + 0.65毫克IMI/千克/天)。随机选择的一半雄性后代在PND29时处死,其余一半不接触并在PND63时处死。研究的各种终点包括脑重量、组织学、血浆激素谱和工作记忆表现。在PND29时,混合物暴露组的脑重量显著下降,并持续到PND63。在IMI和混合物暴露组的CA1和CA3区域,锥体细胞层的总厚度显著降低,同时锥体细胞出现排列不齐、萎缩和退化。在PND29和PND63时,混合物暴露组锥体细胞树突的长度和分支点均显著减少。混合物暴露组后代的树突棘密度也降低。仅在PND29时,睾酮水平显著降低,但在混合物暴露的后代中,PND29和PND63时皮质酮水平均升高。T迷宫任务表现显示,混合物暴露组后代的持续时间显著增加,路径效率降低。因此,结果表明,即使单独使用剂量对海马体组织没有任何不良影响,农药混合物暴露也可能导致学习行为的改变。

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