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亚急性给予苯并(a)芘后成年雌性小鼠的行为及NMDA-R1基因mRNA表达的调节

Modulation of behavior and NMDA-R1 gene mRNA expression in adult female mice after sub-acute administration of benzo(a)pyrene.

作者信息

Grova Nathalie, Valley Anne, Turner Jonathan D, Morel Andrée, Muller Claude P, Schroeder Henri

机构信息

Institute of Immunology, Laboratoire National de Santé, 20A rue Auguste Lumière, L-1011 Luxembourg, Luxembourg.

出版信息

Neurotoxicology. 2007 May;28(3):630-6. doi: 10.1016/j.neuro.2007.01.010. Epub 2007 Feb 2.

Abstract

The behavioral performances of adult mice exposed to sub-acute doses of benzo(a)pyrene (B(a)P) were monitored in tests related to learning and memory (Y maze and Morris water maze), locomotor activity (open-field test) and motor coordination (Locotronic apparatus). At low doses (0.02 and 0.2mg/kg), B(a)P impaired short-term learning and spatial memory performance in the Y maze and in the Morris water maze tests. Surprisingly, in the Y maze, the performances of animals exposed to the highest dose of B(a)P (200mg/kg) were quite similar to those of control animals. Hyperactivity/hyperarousal observed in both tests at this dose and attributed to an anxiolytic-like effect of B(a)P may have blurred the learning deficit in these mice faced with a new situation. These deficits seem to be unrelated to motor impairments because B(a)P had no effect on locomotor activity and motor coordination. We demonstrated that sub-acute exposure to B(a)P in adult mice also modulates gene expression of NMDA-R1 subunit in brain areas highly involved in cognitive function like the hippocampus, suggesting a relationship between the expression of functional NMDA-R1 mRNA, impairment of short-term and spatial memory and the B(a)P exposure levels.

摘要

在与学习和记忆相关的测试(Y迷宫和莫里斯水迷宫)、自发活动(旷场试验)以及运动协调性(Locotronic仪器)中,监测了成年小鼠亚急性剂量接触苯并(a)芘(B(a)P)后的行为表现。在低剂量(0.02和0.2mg/kg)时,B(a)P损害了Y迷宫和莫里斯水迷宫测试中的短期学习和空间记忆表现。令人惊讶的是,在Y迷宫中,接触最高剂量B(a)P(200mg/kg)的动物表现与对照动物相当相似。在此剂量下,两项测试中均观察到的多动/过度觉醒归因于B(a)P的抗焦虑样作用,这可能掩盖了这些面临新情况的小鼠的学习缺陷。这些缺陷似乎与运动障碍无关,因为B(a)P对自发活动和运动协调性没有影响。我们证明,成年小鼠亚急性接触B(a)P还会调节海马体等高度参与认知功能的脑区中NMDA-R1亚基的基因表达,这表明功能性NMDA-R1 mRNA的表达、短期和空间记忆损伤与B(a)P暴露水平之间存在关联。

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