Article

Bisphenol-A Impairs Memory and Reduces Dendritic Spine Density in Adult Male Rats

Department of Psychology, Hunter College, The City University of New York, New York, NY 10065, USA.
Behavioral Neuroscience (Impact Factor: 2.73). 02/2012; 126(1):175-85. DOI: 10.1037/a0025959
Source: PubMed

ABSTRACT

Exposure to Bisphenol-A (BPA), an endocrine disruptor used in plastics, occurs in the United States on a daily basis. Recent studies suggest exposure during development causes memory deficits later in life; however, the ramifications of exposure in adulthood are unclear. We examined the effects of acute BPA administration (40 μg/kg) on memory and synaptic plasticity in adult male rats. BPA significantly impaired both visual and spatial memory and decreased dendritic spine density on pyramidal cells in CA1 and the medial prefrontal cortex (mPFC). Additionally, BPA significantly decreased PSD-95, a synaptic marker, in the hippocampus and increased cytosolic pCREB, a transcription factor, in mPFC. Together, these findings show that a single dose of BPA, below the USEPA reference safe daily limit of 50 μg/kg/day, may block the formation of new memories by interfering with neural plasticity processes in the adult brain.

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    • "Conflicting results, however, have been obtained using such assessments in laboratory rodents exposed to BPA. Some reports have suggested that BPA exposure impairs spatial learning and memory (Diaz Weinstein et al., 2013; Eilam-Stock et al., 2012; Goncalves et al., 2010; Jasarevic et al., 2011, 2013; Kim et al., 2011; Kuwahara et al., 2013; Viberg et al., 2011; Xu et al., 2013); while others suggest minimal or no BPA effects on spatial navigation (Ferguson et al., 2012; Kuwahara et al., 2014; Neese et al., 2013; Ryan and Vandenbergh, 2006; Sadowski et al., 2014a; Williams et al., 2013). Differences in species, age at and/or route of exposure, BPA dose, and testing methods may account for those varying results. "
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    ABSTRACT: Bisphenol A (BPA) is a ubiquitous industrial chemical used in the production of a wide variety of items. Previous studies suggest BPA exposure may result in neuro-disruptive effects; however, data are inconsistent across animal and human studies. As part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA), we sought to determine whether female and male rats developmentally exposed to BPA demonstrated later spatial navigational learning and memory deficits. Pregnant NCTR Sprague-Dawley rats were orally dosed from gestational day 6 to parturition, and offspring were directly orally dosed until weaning (postnatal day 21). Treatment groups included a vehicle control, three BPA doses (2.5μg/kg/day-[2.5], 25μg/kg/day-[25], and 2500μg/kg/day-[2500]) and a 0.5μg/kg/day ethinyl estradiol (EE)-reference estrogen dose. At adulthood, 1/sex/litter was tested for seven days in the Barnes maze. The 2500 BPA group sniffed more incorrect holes on day 7 than those in the control, 2.5 BPA, and EE groups. The 2500 BPA females were less likely than control females to locate the escape box in the allotted time (p value=0.04). Although 2.5 BPA females exhibited a prolonged latency, the effect did not reach significance (p value=0.06), whereas 2.5 BPA males showed improved latency compared to control males (p value=0.04), although the significance of this result is uncertain. No differences in serum testosterone concentration were detected in any male or female treatment groups. Current findings suggest developmental exposure of rats to BPA may disrupt aspects of spatial navigational learning and memory.
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    • "Behavioral measures were performed in designated behavioral testing rooms (21.1 °C, 43 lm/square meter) and all behavioral testing occurred between 9:00 and 14:00 h. Behavioral measures were obtained in real time by trained laboratory researchers who were blind to treatment assignment consistent with past studies (Bowman and Kelly, 2012; Bowman et al., 2001, 2002; Diaz Wienstein et al., 2013; Eilam-Stock et al., 2012). In addition, a paired sample t-test was conducted on open field measures scored in real-time versus from video for a group of animals (not otherwise used in the study, n = 5) and there are no differences between the two (see Table 2). "
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    ABSTRACT: We have previously demonstrated that adolescent exposure of rats to bisphenol-A (BPA), an environmental endocrine disrupter, increases anxiety, impairs spatial memory, and decreases dendritic spine density in the CA1 region of the hippocampus (CA1) and medial prefrontal cortex (mPFC) when measured in adolescence in both sexes. The present study examined whether the behavioral and morphological alterations following BPA exposure during adolescent development are maintained into adulthood. Male and female, adolescent rats received BPA, 40μg/kg/bodyweight, or control treatments for one week. In adulthood, subjects were tested for anxiety and locomotor activity, spatial memory, non-spatial visual memory, and sucrose preference. Additionally, stress-induced serum corticosterone levels and dendritic spine density in the mPFC and CA1 were measured. BPA-treated males, but not females, had decreased arm visits on the elevated plus maze, but there was no effect on anxiety. Non-spatial memory, object recognition, was also decreased in BPA treated males, but not females. BPA exposure did not alter spatial memory, object placement, but decreased exploration during the tasks in both sexes. No significant group differences in sucrose preference or serum corticosterone levels in response to a stress challenge were found. However, BPA exposure, regardless of sex, significantly decreased spine density of both apical and basal dendrites on pyramidal cells in CA1 but had no effect in the mPFC. Current data are discussed in relation to BPA dependent changes, which were present during adolescence and did, or did not, endure into adulthood. Overall, adolescent BPA exposure, below the current reference safe daily limit set by the U.S.E.P.A., leads to alterations in some behaviors and neuronal morphology that endure into adulthood. Copyright © 2014. Published by Elsevier Inc.
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    • "h prior to sacrifice. Animals were sacrificed via rapid decapitation and mammary gland tissue was collected from each rat, flash frozen on dry ice, and then stored at −80 • C until RNA extraction [65] [66] [104] "
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    ABSTRACT: Antisense transcript, long non-coding RNA HOTAIR is a key player in gene silencing and breast cancer and is transcriptionally regulated by estradiol. Here, we have investigated if HOTAIR expression is misregulated by bisphenol-A (BPA) and diethylstilbestrol (DES). Our findings demonstrate BPA and DES induce HOTAIR expression in cultured human breast cancer cells (MCF7) as well as in vivo in the mammary glands of rat. Luciferase assay showed that HOTAIR promoter estrogen-response-elements (EREs) are induced by BPA and DES. Estrogen-receptors (ERs) and ER-coregulators such as MLL-histone methylases (MLL1 and MLL3) bind to the HOTAIR promoter EREs in the presence of BPA and DES, modify chromatin (histone methylation and acetylation) and lead to gene activation. Knockdown of ERs down-regulated the BPA and DES induced expression of HOTAIR. In summary, our results demonstrate that BPA and DES exposure alters the epigenetic programming of the HOTAIR promoters leading to its endocrine disruption in vitro and in vivo.
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