Prenatal and postnatal exposure to bisphenol a induces anxiolytic behaviors and cognitive deficits in mice

Abstract

Bisphenol A (BPA), an environmental endocrine-disrupting chemical, has been extensively evaluated for reproductive toxicity and carcinogenicity. However, little is known about the behavioral and neurochemical effects of BPA exposure. This study examined whether chronic daily exposure to an environmental endocrine-disrupting chemical, bisphenol A [(BPA); 100 microg/kg/day or 500 microg/kg/day, p.o.], from prenatal Day 7 to postnatal Day 36 would lead to changes in anxiety and memory in mice. First, we observed the behavioral alterations of BPA-treated mice using two anxiety-related models, the open field test and elevated plus maze (EPM) test. In the open field test, BPA treatment (100 microg/kg/day) increased movement in the central zone. BPA treatment (500 microg/kg/day) also increased the time spent in the open arms in the EPM test. Second, we measured cognitive ability in the Y-maze test and novel object test. BPA-treated mice showed decreased alternation behavior in the Y-maze at both of doses, indicating working memory impairment. BPA-treated mice (100 microg/kg/day) also showed decreased novel object recognition as expressed by central locomotion and frequency in the central zone, showing recognition memory impairment. Finally, to measure changes in the dopaminergic and NMDAergic systems in the brain, we performed autoradiographic receptor binding assays for dopamine D(1) and D(2) receptors, the NMDA receptor, and the dopamine transporter. BPA treatment increased D(2) receptor binding in the caudate putamen (CPu) but decreased DAT binding. BPA treatment also decreased NMDA receptor binding in the frontal cortex and CA1, CA3, and DG of the hippocampus. Taken together, our results suggest that long-term BPA exposure in mice can induce anxiolytic behaviors, cognitive deficits and changes in the dopaminergic and NMDAergic systems.

Impact of Early-Life Bisphenol A Exposure on Behavior and Executive Function in Children

“…14,38 Gestational BPA exposures might affect endocrine or other neurotransmitter pathways and disrupt sexual differentiation of the brain, to alter behavior in a genderdependent manner. 39,40 However, the exposures and behavioral end points used in some animal studies might not be relevant or comparable to human cases.…”

“…11 Experimental studies with animals indicated that gestational BPA exposure disrupts normal neurodevelopment, affecting sexually dimorphic behaviors such as aggression, anxiety, exploration, and spatial memory. [12][13][14] Sexually dimorphic clinical disorders such as attention-deficit/hyperactivity disorder, autism, and depression might be clinical correlates of these animal behaviors and might be related to early-life disruption of the endocrine system. 15,16 These observations suggest that sexually dimorphic behavioral traits may serve as sensitive end points in epidemiological studies.…”

Effects of Bisphenol A on ion channels: Experimental evidence and molecular mechanisms

“…Later, in 2010, two papers reported a decrease of NMDA receptors in mice hippocampus. Prenatal and postnatal exposure to BPA at low doses (100-500 µg/Kg/day) decreased NMDA (not subtype specified) and dopamine receptors, and induced anxiolytic behaviors as well as cognitive deficits [45]. At high doses (50-50000 µg/Kg/day) BPA inhibited the expression of NMDA receptors GluN1, GluN2A and GluN2B and ERβ, impairing learning and memory [46] That same year, two other papers reported opposite effects of low doses of BPA on NMDA receptors in rat hippocampus: a decrease in the expression of NMDA receptors [47] and an increase in NMDA receptors GluN2B mediated by ERβ phosphorylation promoting dynamic changes in hippocampal dendritic morphology [48] A further paper by Xu and coworkers reported again an increase in the expression of NMDA receptors GluN1and…”

May BPA and phthalates have a role in etiopathogenesis of ADHD?

“…Experimental studies with animals indicated that gestational BPA exposure disrupts normal neurodevelopment, affecting aggression, anxiety, exploration, and spatial memory. 23,24 BPA exposure also induces prefrontal and hippocampal spin synapse loss in rodents which may result in cognitive dysfunction. 25 The animal literature suggests that exposure to BPA affects the development of the forebrain dopaminergic system via binding to estrogen dependent dopaminergic receptors that are important for regulation of behavioral impulses.…”