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双酚A以性别依赖性方式损害小鼠的记忆功能和谷氨酸能稳态:二苯基二硒醚的有益作用。

Bisphenol A impairs the memory function and glutamatergic homeostasis in a sex-dependent manner in mice: Beneficial effects of diphenyl diselenide.

作者信息

Jardim Natália S, Sartori Glaúbia, Sari Marcel H M, Müller Sabrina G, Nogueira Cristina W

机构信息

Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil.

Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil.

出版信息

Toxicol Appl Pharmacol. 2017 Aug 15;329:75-84. doi: 10.1016/j.taap.2017.05.035. Epub 2017 May 29.

Abstract

Bisphenol A (BPA) is a compound integrated in commodities, which consequently increases the human exposure to this toxicant. The deleterious effects of BPA exposure during periods of brain development have been documented mainly concerning the impairment in memory functions. Diphenyl diselenide (PhSe), an organoselenium compound, shows protective/restorative effects against memory deficits in experimental models. Thus, this study investigated the effects of (PhSe) on the memory impairments induced by BPA exposure to male and female mice and the possible involvement of glutamatergic system in these effects. Three-week-old male and female Swiss mice received BPA (5mg/kg), intragastrically, from 21st to 60th postnatal day. After, the animals were intragastrically treated with (PhSe) (1mg/kg) during seven days. The mice performed the behavioral memory tests and the [H] glutamate uptake and NMDA receptor subunits (2A and 2B) analyses were carried out in the hippocampus and cerebral cortex of mice. The results demonstrated that the BPA exposure induced impairment of object recognition memory in both sexes. However, it caused impairments in spatial memory in female and in the passive avoidance memory in male mice. Besides, BPA caused a decrease in the [H] glutamate uptake and NMDA receptor subunit levels in the cortical and hippocampal regions depending on the sex. Treatment with (PhSe) reversed in a sex-independent manner the behavioral impairments and molecular alterations. In conclusion, BPA had a negative effect in different memory types as well as in the glutamatergic parameters in a sex-dependent manner and (PhSe) treatment was effective against these alterations.

摘要

双酚A(BPA)是一种存在于商品中的化合物,这导致人类对这种有毒物质的接触增加。脑发育期间接触BPA的有害影响主要记录在记忆功能受损方面。二苯基二硒醚(PhSe)是一种有机硒化合物,在实验模型中显示出对记忆缺陷的保护/恢复作用。因此,本研究调查了(PhSe)对BPA暴露诱导的雄性和雌性小鼠记忆损伤的影响,以及谷氨酸能系统在这些影响中可能的参与情况。三周龄的雄性和雌性瑞士小鼠在出生后第21天至60天经口给予BPA(5mg/kg)。之后,动物在七天内经口给予(PhSe)(1mg/kg)。小鼠进行行为记忆测试,并在小鼠的海马体和大脑皮层中进行[H]谷氨酸摄取和NMDA受体亚基(2A和2B)分析。结果表明,BPA暴露导致两性的物体识别记忆受损。然而,它导致雌性小鼠的空间记忆受损和雄性小鼠的被动回避记忆受损。此外,BPA导致皮质和海马区域中[H]谷氨酸摄取和NMDA受体亚基水平根据性别而降低。用(PhSe)治疗以与性别无关的方式逆转了行为损伤和分子改变。总之,BPA对不同类型的记忆以及谷氨酸能参数有性别依赖性的负面影响,而(PhSe)治疗对这些改变有效。

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