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Bisphenol A prevents the synaptogenic response to estradiol in hippocampus and prefrontal cortex of ovariectomized nonhuman primates

Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 10/2008; 105(37):14187-91. DOI: 10.1073/pnas.0806139105
Source: PubMed

ABSTRACT Exposure measurements from several countries indicate that humans are routinely exposed to low levels of bisphenol A (BPA), a synthetic xenoestrogen widely used in the production of polycarbonate plastics. There is considerable debate about whether this exposure represents an environmental risk, based on reports that BPA interferes with the development of many organs and that it may alter cognitive functions and mood. Consistent with these reports, we have previously demonstrated that BPA antagonizes spine synapse formation induced by estrogens and testosterone in limbic brain areas of gonadectomized female and male rats. An important limitation of these studies, however, is that they were based on rodent animal models, which may not be representative of the effects of human BPA exposure. To address this issue, we examined the influence of continuous BPA administration, at a daily dose equal to the current U.S. Environmental Protection Agency's reference safe daily limit, on estradiol-induced spine synapse formation in the hippocampus and prefrontal cortex of a nonhuman primate model. Our data indicate that even at this relatively low exposure level, BPA completely abolishes the synaptogenic response to estradiol. Because remodeling of spine synapses may play a critical role in cognition and mood, the ability of BPA to interfere with spine synapse formation has profound implications. This study is the first to demonstrate an adverse effect of BPA on the brain in a nonhuman primate model and further amplifies concerns about the widespread use of BPA in medical equipment, and in food preparation and storage.

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Available from: Csaba Leranth, Aug 29, 2015
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    • "While BPA is generally less potent than estradiol for ER, it is equipotent with estradiol in activating rapid signaling systems via non-nuclear receptors (Watson et al., 2007). BPA is generally considered an ER agonist, but it can also antagonize the actions of estrogens in certain tissues, including the brain and uterus (Leranth et al., 2008a,b). BPA thus has mixed agonist/antagonist activity and is considered a selective estrogen receptor modulator (Nagel et al., 2001). "
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    • "While BPA is generally less potent than estradiol for ER, it is equipotent with estradiol in activating rapid signaling systems via non-nuclear receptors (Watson et al., 2007). BPA is generally considered an ER agonist, but it can also antagonize the actions of estrogens in certain tissues, including the brain and uterus (Leranth et al., 2008a,b). BPA thus has mixed agonist/antagonist activity and is considered a selective estrogen receptor modulator (Nagel et al., 2001). "
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    • "While BPA is generally less potent than estradiol for ER, it is equipotent with estradiol in activating rapid signaling systems via non-nuclear receptors (Watson et al., 2007). BPA is generally considered an ER agonist, but it can also antagonize the actions of estrogens in certain tissues, including the brain and uterus (Leranth et al., 2008a,b). BPA thus has mixed agonist/antagonist activity and is considered a selective estrogen receptor modulator (Nagel et al., 2001). "
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