Memory Function, Neurological, and Immunological Biomarkers in Allergic Asthmatic Mice Intratracheally Exposed to Bisphenol A

Abstract

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.

Dietary exposure to bisphenol A affects memory function and neuroimmune biomarkers in allergic asthmatic mice

“…Allergic asthma can cause brain hypoxia, and dietary BPA exposure during the adolescent period may induce inflammatory responses in the brain and which in turn induce memory impairment via modulation of the hippocampal memory function‐related genes NMDA receptor in mice of allergic asthmatic animal models. Recently, we have reported that intratracheal instillation of BPA (25 pmol BPA per mouse for 6 weeks) in the adolescent period impairs object recognition ability and causes no change of brain and immune biomarkers in OVA‐immunized mice (Win‐Shwe et al, 2019). We suggest that dose, duration, route, and exposure schedule may influence BPA exposure on neuroimmune interaction in allergic asthmatic mice.…”

“…Timing of exposure, route of administration, and exposure schedule may influence the dose–response effects. Our recent study has shown that intratracheal instillation of BPA‐H impaired memory function accompanied with changes in NMDA receptor but no associated with inflammatory markers in the brain of allergic asthmatic mice (Win‐Shwe et al, 2019). In this study, we aimed to examine whether dietary BPA exposure during the adolescent period has an impact on higher brain function and biomarkers such as NMDA receptor NR1, NR2A and NR2B, IL‐1 β, TNF‐α, ionized calcium‐binding adapter molecule (Iba)‐1, cyclooxygenase‐2 (COX2), and HO‐1 in a mouse model with allergy.…”

“…Some asthmatic patients showed cognitive deficit and marked shrinkage of hippocampal volume suggesting that association exists between asthma and brain function (Carlson et al, 2017). Recently, we have reported that intratracheal instillation of BPA‐H induced poor memory function via memory function‐related gene N‐methyl‐D‐aspartate (NMDA) receptor in the hippocampus of mice (Win‐Shwe et al, 2019). Our previous study showed that phthalate di‐(2‐ethylhexyl) phthalate (DEHP) exposure during adolescence induced neuroinflammation via neuroimmune biomarkers such as interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α, the chemokine CCL3, the transcription factor nuclear factor (NF)‐κB, and the oxidative stress marker heme‐oxygenase (HO)1 were remarkably up‐regulated in the hypothalami of allergic asthma mice (Win‐Shwe et al, 2013).…”

Dietary Exposure to Flame Retardant Tris (2-Butoxyethyl) Phosphate Altered Neurobehavior and Neuroinflammatory Responses in a Mouse Model of Allergic Asthma

“…Briefly, asthma may induce brain hypoxia and cause inflammatory responses via neuro-immune molecular markers, which induce cognitive impairment via hippocampal memory function-related genes. We have reported that exposure to environmental chemicals enhanced these effects [ 12 , 13 , 14 ]. A recent study has also demonstrated that asthma-induced brain hypoxia caused the impairment of learning and memory via dysfunction of synaptic tissues and blood vessels, increased levels of hypoxia-inducible factors marker Hif-1α and Hif-2α [ 15 ].…”

Investigation of the effects of bisphenol-A exposure on lymphoid system in prenatal stage

“…Therefore, BPA affects estrogen receptor functions and also other nuclear hormone receptors (Fenichel et al, 2013). In recent years, exposure to BPA has been associated with a wide range of metabolic, reproductive, cardiovascular and neurological diseases and also with increased incidences of endocrine diseases and endocrine-related cancers (Dunder et al, 2019;Friques et al, 2020;Hafezi and Abdel-Rahman, 2019;Hu et al, 2019;Khan et al, 2019;Piao et al, 2019;Santoro et al, 2019;Shu et al, 2019;Win-Shwe et al, 2019). These effects are mediated by hormonal regulation and metabolic signals, mainly by nuclear receptors, or by mechanisms that are currently unknown.…”