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 Yale School of Medicine researchers reported today that the chemical bisphenol-A (BPA), a building block for polycarbonate plastics found in common household items, causes the loss of connections between brain cells. This synaptic loss may cause memory/learning impairments and depression, according to study results published in the Proceedings of the National Academy of Sciences (PNAS).
Unlike previous studies that looked at the effect of BPA on rodents, the team examined the effects in a primate model. They also used lower levels of the chemical than in past studies. “Our goal was to more closely mimic the slow and continuous conditions under which humans would normally be exposed to BPA,” said study author Csaba Leranth, M.D., professor in the Department of Obstetrics, Gynecology & Reproductive Sciences and in Neurobiology at Yale. “As a result, this study is more indicative than past research of how BPA may actually affect humans.”
Over a 28-day period, Leranth and his team gave each primate 50 micrograms/kg of BPA per day, adjusted for body weight, the amount considered safe for human consumption by the Environmental Protection Agency (EPA). The team also administered estradiol, the major form of hormonal estrogen that modulates nerve cell connections in the brain. Best known as one of the principal hormone products of the ovary, estrogen has also been shown in past studies to be synthesized in the brain, where it aids the development and function of the hippocampus and prefrontal cortex.
The team then used an electron microscope to count nerve cell connections in the brain. They found that BPA inhibits creation of the synaptic connections in the hippocampus and prefrontal cortex, areas of the brain involved with regulation of mood and formation of memory.
“Our primate model indicates that BPA could negatively affect brain function in humans,” said study co-author Tibor Hajszan, M.D., associate research scientist in Yale Ob/Gyn. “Based on these new findings, we think the EPA may wish to consider lowering its ‘safe daily limit’ for human BPA consumption.”
Hajszan said that although daily exposure of an average person to BPA usually does not reach the level that was applied in this study, human exposure to BPA is not limited to a single month, but rather is continuous over a lifetime. “The negative effect of BPA may also be amplified when estradiol levels are naturally lower than in healthy adults. That is why exposure to BPA may particularly be risky in the case of babies and the elderly.”
Other authors on the study included Klara Szigeti-Buck, Jeremy Bober and Neil J. MacLusky.
The study was supported by the National Institutes of Health and by a National Alliance for Research on Schizophrenia and Depression Young Investigator Award.
Citation: PNAS Online Early Edition, 10.1073/pnas.0806139105 (September 2, 2008)
Bisphenol A prevents the synaptogenic response to estradiol in hippocampus and prefrontal cortex of ovariectomized nonhuman primates
 http://www.pnas.org/content/early/2008/09/02/0806139105.abstract
by Csaba Leranth*,†,‡, Tibor Hajszan*, Klara Szigeti-Buck*,§, Jeremy Bober*, and Neil J. MacLusky¶
Author Affiliations
1. Departments of *Obstetrics, Gynecology, and Reproductive Sciences;
2. †Neurobiology, and
3. §Pharmacology, Yale University School of Medicine, New Haven, CT 06520; and
4. ¶Department of Biomedical Sciences, Ontario Veterinary College, Guelph, ON, Canada N1G 2W1
Edited by Bruce S. McEwen, The Rockefeller University, New York, NY, and approved July 14, 2008 (received for review June 25, 2008)
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.
Footnotes
- The authors declare no conflict of interest.
- This article is a PNAS Direct Submission.
© 2008 by The National Academy of Sciences of the USA.
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