Win-Shwe Tin-Tin, Yanagisawa Rie, Koike Eiko, Takano Hirohisa
Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, Japan.
Graduate School of Global Environmental Studies, Kyoto University, Kyoto, Japan.
J Appl Toxicol. 2021 Oct;41(10):1527-1536. doi: 10.1002/jat.4143. Epub 2021 Jan 20.
Bisphenol A (BPA) is a raw material of polycarbonate and epoxy resin. It is used for various household electrical appliances, electronic equipment, office automation equipment, medical equipment, mobile phones, paints for automobiles, internal surface coating of cans, and adhesives for civil engineering and construction. BPA is a well-known endocrine-disrupting chemical, and it was reported that BPA has an adverse effect on the nervous and immune systems. However, BPA-induced memory impairment and changes in neuroimmune biomarkers in the allergic asthmatic subject are not known yet. We aim to investigate the dietary exposure effect of BPA on brain function and biomarkers using allergic an asthmatic mouse model. Five-week-old male C3H/HeJSlc mice were fed two doses of BPA [0.901, 9.01 μg/kg/day] contained chow diet from 5 to 11 weeks old and ovalbumin (OVA) was given by intratracheal instillation every 2 weeks. Memory function was determined by a novel object recognition test. Genes related to memory and immune markers in the hippocampus were investigated with the real-time polymerase chain reaction (RT-PCR) method. In this study, impaired novel object recognition occurred in BPA-exposed mice in the presence of an allergen. Moreover, upregulation of expression level of neuroimmune biomarkers such as N-methyl-D-aspartate receptor, tumor necrosis factor-α, ionized calcium-binding adapter molecule-1, cyclooxygenase-2, and heme oxygenase-1 in the hippocampus was observed in BPA-exposed allergic asthmatic mice. These findings show that BPA exposure can induce neuroinflammation and which triggers impairment of memory function in mice with allergic asthma. Our study indicated that dietary exposure to BPA may affect higher brain functions by modulating neuroimmune biomarkers in allergic asthmatic subjects.
双酚A（BPA）是聚碳酸酯和环氧树脂的原材料。它被用于各种家用电器、电子设备、办公自动化设备、医疗设备、手机、汽车涂料、罐头内表面涂层以及土木工程和建筑用胶粘剂。双酚A是一种著名的内分泌干扰化学物质，据报道它对神经和免疫系统有不良影响。然而，双酚A对过敏性哮喘患者的记忆损害和神经免疫生物标志物变化尚不清楚。我们旨在使用过敏性哮喘小鼠模型研究双酚A的饮食暴露对脑功能和生物标志物的影响。5周龄雄性C3H/HeJSlc小鼠从5周龄到11周龄喂食含有两种剂量双酚A[0.901、9.01μg/kg/天]的饲料，每2周通过气管内滴注给予卵清蛋白（OVA）。通过新颖物体识别测试确定记忆功能。采用实时聚合酶链反应（RT-PCR）方法研究海马中与记忆和免疫标志物相关的基因。在本研究中，在存在过敏原的情况下，暴露于双酚A的小鼠出现新颖物体识别受损。此外，在暴露于双酚A的过敏性哮喘小鼠中，观察到海马中神经免疫生物标志物如N-甲基-D-天冬氨酸受体、肿瘤坏死因子-α、离子钙结合衔接分子-1、环氧合酶-2和血红素加氧酶-1的表达水平上调。这些发现表明，双酚A暴露可诱导神经炎症，进而引发过敏性哮喘小鼠的记忆功能损害。我们的研究表明，饮食中暴露于双酚A可能通过调节过敏性哮喘患者的神经免疫生物标志物来影响高级脑功能。
