Developmental subchronic exposure to diphenylarsinic acid induced increased exploratory behavior, impaired learning behavior, and decreased cerebellar glutathione concentration in rats.
Developmental subchronic exposure to diphenylarsinic acid induced increased exploratory behavior, impaired learning behavior, and decreased cerebellar glutathione concentration in rats.
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DOI：
10.1093/toxsci/kft200
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发表时间：
2013-12
期刊：
影响因子：
--
通讯作者：
Tashiro T
中科院分区：
文献类型：
--
作者：
Negishi T;Matsunaga Y;Kobayashi Y;Hirano S;Tashiro T
在日本，人们使用被高浓度砷污染的井中的水后出现了神经症状，主要是小脑症状，其中二苯胂酸 (DPAA) 是主要化合物。在此，我们研究了雄性大鼠在发育过程中暴露于饮用水中的 20mg/l DPAA（早期 [0-6 周龄] 和/或晚期 [7-12]）对行为和小脑发育的不利影响。在 6 周龄的旷场测试中，早期接触 DPAA 显着增加了探索行为。在 12 周龄时，后期接触 DPAA 类似地增加了探索行为，与早期接触无关，尽管 6 周恢复 DPAA 可以逆转这种变化。在6周龄的被动回避测试中，早期接触DPAA显着降低了回避表现。即使在 12 周龄时，早期接触 DPAA 也会显着降低测试成绩，这与后期接触 DPAA 无关。这些结果表明，DPAA 引起的探索行为的增加是短暂的，而 DPAA 引起的被动回避损害是长期持续的。 6 周龄时，早期接触 DPAA 显着降低了小脑总谷胱甘肽的浓度。在 12 周龄时，晚但不是早，暴露于 DPAA 也显着降低了小脑谷胱甘肽的浓度，这可能是氧化应激的主要原因。早期暴露于 DPAA 会导致 12 周龄时 NMDAR1 和 PSD95 蛋白的迟发性抑制表达，表明发育暴露于 DPAA 的大鼠小脑中谷氨酸能系统受损。
In Japan, people using water from the well contaminated with high-level arsenic developed neurological, mostly cerebellar, symptoms, where diphenylarsinic acid (DPAA) was a major compound. Here, we investigated the adverse effects of developmental exposure to 20mg/l DPAA in drinking water (early period [0–6 weeks of age] and/or late period [7–12]) on behavior and cerebellar development in male rats. In the open field test at 6 weeks of age, early exposure to DPAA significantly increased exploratory behaviors. At 12 weeks of age, late exposure to DPAA similarly increased exploratory behavior independent of the early exposure although a 6-week recovery from DPAA could reverse that change. In the passive avoidance test at 6 weeks of age, early exposure to DPAA significantly decreased the avoidance performance. Even at 12 weeks of age, early exposure to DPAA significantly decreased the test performance, which was independent of the late exposure to DPAA. These results suggest that the DPAA-induced increase in exploratory behavior is transient, whereas the DPAA-induced impairment of passive avoidance is long lasting. At 6 weeks of age, early exposure to DPAA significantly reduced the concentration of cerebellar total glutathione. At 12 weeks of age, late, but not early, exposure to DPAA also significantly reduced the concentration of cerebellar glutathione, which might be a primary cause of oxidative stress. Early exposure to DPAA induced late-onset suppressed expression of NMDAR1 and PSD95 protein at 12 weeks of age, indicating impaired glutamatergic system in the cerebellum of rats developmentally exposed to DPAA.
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影响因子：
3.9
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Kinoshita, K;Shida, Y;Kaise, T
通讯作者：
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