Center for Health and Environmental Risk Research, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan.
Environmental Health Sciences, Graduate School of Global Environmental Studies, Kyoto University, Kyoto 615-8540, Japan.
Int J Environ Res Public Health. 2019 Oct 8;16(19):3770. doi: 10.3390/ijerph16193770.
Bisphenol A (BPA) is a major constituent of plastic products, including epoxy resin containers, mobile phones, dental sealants, as well as electronic and medical equipment. BPA is recognized as an endocrine system-disrupting chemical which has toxic effects on the brain and reproductive system. However, little is known about the effects of co-exposure of BPA with allergens on the memory function and neurological as well as immunological biomarker levels. In this study, we examined the effects of intratracheal instillation of BPA on the memory function and neuroimmune biomarker levels using a mouse model of allergic asthma. Male C3H/HeJ Jcl mice were given three doses of BPA (0.0625 pmol, 1.25 pmol, and 25 pmol BPA/animal) intratracheally once a week, and ovalbumin (OVA) intratracheally every other week from 5 to 11 weeks old. At 11 weeks of age, a novel object recognition test was conducted after the final administration of OVA, and the hippocampi and hypothalami of the animals were collected after 24 h. The expression levels of the memory function-related genes N-methyl-D-aspartate (NMDA) receptor subunits, inflammatory cytokines, microglia markers, estrogen receptor-alpha, and oxytocin receptor were examined by real-time RT-PCR (real-time reverse transcription polymerase chain reaction) and immunohistochemical methods. Impairment of the novel object recognition ability was observed in the high-dose BPA-exposed mice with allergic asthma. In addition, the allergic asthmatic mice also showed downregulation of neurological biomarkers, such as NMDA receptor subunit NR2B in the hippocampus but no significant effect on immunological biomarkers in the hypothalamus. These findings suggest that exposure to high-dose BPA triggered impairment of memory function in the allergic asthmatic mice. This is the first study to show that, in the presence of allergens, exposure to high-dose BPA may affect memory by modulating the memory function-related genes in the hippocampus.
双酚 A（BPA）是塑料产品的主要成分之一，包括环氧树脂容器、手机、牙密封剂以及电子和医疗设备。BPA 被认为是一种内分泌系统干扰化学物质，对大脑和生殖系统具有毒性作用。然而，对于 BPA 与过敏原共同暴露对记忆功能以及神经和免疫生物标志物水平的影响知之甚少。在这项研究中，我们使用过敏性哮喘小鼠模型研究了经气管内滴注 BPA 对记忆功能和神经免疫生物标志物水平的影响。雄性 C3H/HeJ Jcl 小鼠每周一次经气管内给予 3 次 BPA（0.0625 pmol、1.25 pmol 和 25 pmol BPA/动物），并且从 5 至 11 周龄每隔一周经气管内给予卵清蛋白（OVA）。在最后一次给予 OVA 后 24 小时，进行新物体识别测试，收集动物的海马体和下丘脑。通过实时 RT-PCR（实时逆转录聚合酶链反应）和免疫组织化学方法检测与记忆功能相关的基因 N-甲基-D-天冬氨酸（NMDA）受体亚基、炎性细胞因子、小胶质细胞标志物、雌激素受体-α和催产素受体的表达水平。在具有过敏性哮喘的高剂量 BPA 暴露小鼠中观察到新物体识别能力受损。此外，过敏性哮喘小鼠的下丘脑免疫生物标志物也没有明显变化，但海马体中的 NMDA 受体亚基 NR2B 等神经生物标志物表达下调。这些发现表明，暴露于高剂量 BPA 会触发过敏性哮喘小鼠记忆功能受损。这是第一项表明在存在过敏原的情况下，暴露于高剂量 BPA 可能通过调节海马体中与记忆功能相关的基因来影响记忆的研究。
