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


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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    • "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.
    Hormones and Behavior 12/2014; 69. DOI:10.1016/j.yhbeh.2014.12.007 · 4.63 Impact Factor
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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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    • "Most research has focused on the neurotoxic effects associated with perinatal exposure to BPA and the mechanism of action behind these neuro-developmental effects [9]. Although recent works point out to adverse effects of BPA on adult brain [10], [11], there is still limited toxicogenomic information on BPA-induced neurotoxicity during adult life. "
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    ABSTRACT: Several neurological and behavioral dysfunctions have been reported in animals exposed to bisphenol A (BPA). However, little is known about the impact of adult exposure to BPA on brain physiopathology. Here, we focused on prefrontal cortex (PFC) of rats, because it is an important area for cognitive control, complex behaviors and is altered in many psychopathologies. Gamma-aminobutyric acid (GABA) and serotonin (5-HT) systems are essential for PFC function. Therefore, we examined the effects of adult exposure to BPA on 5α-Reductase (5α-R) and cytochrome P450 aromatase (P450arom), enzymes that synthesize GABAA receptor modulators, and tryptophan hydroxylase (Tph), the rate-limiting enzyme in 5-HT biosynthesis. To gain better understanding of BPA's action in the adult PFC, 84 genes involved in neurotoxicity were also analysed. Adult male and female rats were subcutaneously injected for 4 days with 50 µg/kg/day, the current reference safe dose for BPA. mRNA and protein levels of 5α-R, P450arom and Tph were quantified by real-time RT-PCR and Western blot. Genes linked to neurotoxicity were analyzed by PCR-Array technology. Adult exposure to BPA increased both P450arom and Tph2 expression in PFC of male and female, but decreased 5α-R1 expression in female. Moreover, we identified 17 genes related to PFC functions such as synaptic plasticity and memory, as potential targets of BPA. Our results provided new insights on the molecular mechanisms underlying BPA action in the physiopathology of PFC, but also raise the question about the safety of short-term exposure to it in the adulthood.
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