Grova Nathalie, Valley Anne, Turner Jonathan D, Morel Andrée, Muller Claude P, Schroeder Henri
Institute of Immunology, Laboratoire National de Santé, 20A rue Auguste Lumière, L-1011 Luxembourg, Luxembourg.
Neurotoxicology. 2007 May;28(3):630-6. doi: 10.1016/j.neuro.2007.01.010. Epub 2007 Feb 2.
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.
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。