The Environmental Estrogen Bisphenol a Inhibits Estradiol-induced Hippocampal Synaptogenesis

Overview

Journal Environ Health Perspect

Date 2005 Jun 3

PMID 15929888

Citations 74

Authors

Neil J MacLusky

Tibor Hajszan

Csaba Leranth

Affiliations

Soon will be listed here.

Abstract

Bisphenol A (BPA) is an estrogenic chemical that is widely used in the manufacture of plastics and epoxy resins. Because BPA leaches out of plastic food and drink containers, as well as the BPA-containing plastics used in dental prostheses and sealants, considerable potential exists for human exposure to this compound. In this article we show that treatment of ovariectomized rats with BPA dose-dependently inhibits the estrogen-induced formation of dendritic spine synapses on pyramidal neurons in the CA1 area of the hippocampus. Significant inhibitory effects of BPA were observed at a dose of only 40 microg/kg, below the current U.S. Environmental Protection Agency reference daily limit for human exposure. Because synaptic remodeling has been postulated to contribute to the rapid effects of estrogen on hippocampus-dependent memory, these data suggest that environmental BPA exposure may interfere with the development and expression of normal sex differences in cognitive function, via inhibition of estrogen-dependent hippocampal synapse formation. It may also exacerbate the impairment of hippocampal function observed during normal aging, as endogenous estrogen production declines.

Citing Articles

Prenatal bisphenol A and/or diethylhexyl phthalate exposure followed by adult estradiol treatment affects behavior and brain monoamines in female rat offspring.

Kaimal A, Hooversmith J, Al Mansi M, Cherry A, Garrity J, Holmes P Front Endocrinol (Lausanne). 2025; 15():1479838.

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Epigenetic Changes in the HTR8 and 3A-sub E placental Cell Lines Exposed to Bisphenol A and Benzyl Butyl Phthalate.

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Bisphenol A Effects on Neurons' Neurochemical Character in the Urinary Bladder Intramural Ganglia of Domestic Pigs.

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The Comparison of the Influence of Bisphenol A (BPA) and Its Analogue Bisphenol S (BPS) on the Enteric Nervous System of the Distal Colon in Mice.

Makowska K, Lepiarczyk E, Gonkowski S Nutrients. 2023; 15(1).

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Perinatal Exposure of Bisphenol A Differently Affects Dendritic Spines of Male and Female Grown-Up Adult Hippocampal Neurons.

Kawato S, Ogiue-Ikeda M, Soma M, Yoshino H, Kominami T, Saito M Front Neurosci. 2021; 15:712261.

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References

Yaffe K, Lui L, Grady D, Cauley J, Kramer J, Cummings S . Cognitive decline in women in relation to non-protein-bound oestradiol concentrations. Lancet. 2000; 356(9231):708-12. DOI: 10.1016/S0140-6736(00)02628-3. View

Toran-Allerand C, Singh M, Setalo Jr G . Novel mechanisms of estrogen action in the brain: new players in an old story. Front Neuroendocrinol. 1999; 20(2):97-121. DOI: 10.1006/frne.1999.0177. View

Wade C, Robinson S, Shapiro R, Dorsa D . Estrogen receptor (ER)alpha and ERbeta exhibit unique pharmacologic properties when coupled to activation of the mitogen-activated protein kinase pathway. Endocrinology. 2001; 142(6):2336-42. DOI: 10.1210/endo.142.6.8071. View

Bi R, Foy M, Vouimba R, Thompson R, Baudry M . Cyclic changes in estradiol regulate synaptic plasticity through the MAP kinase pathway. Proc Natl Acad Sci U S A. 2001; 98(23):13391-5. PMC: 60881. DOI: 10.1073/pnas.241507698. View

Ashby J . Increasing the sensitivity of the rodent uterotrophic assay to estrogens, with particular reference to bisphenol A. Environ Health Perspect. 2001; 109(11):1091-4. PMC: 1240467. DOI: 10.1289/ehp.011091091. View

Suzuki K, Ishikawa K, Sugiyama K, Furuta H, Nishimura F . Content and release of bisphenol A from polycarbonate dental products. Dent Mater J. 2002; 19(4):389-95. DOI: 10.4012/dmj.19.389. View

McEwen B . Estrogen actions throughout the brain. Recent Prog Horm Res. 2002; 57:357-84. DOI: 10.1210/rp.57.1.357. View

Leranth C, Shanabrough M, Redmond Jr D . Gonadal hormones are responsible for maintaining the integrity of spine synapses in the CA1 hippocampal subfield of female nonhuman primates. J Comp Neurol. 2002; 447(1):34-42. DOI: 10.1002/cne.10230. View

Degen G, Janning P, Wittsiepe J, Upmeier A, Bolt H . Integration of mechanistic data in the toxicological evaluation of endocrine modulators. Toxicol Lett. 2002; 127(1-3):225-37. DOI: 10.1016/s0378-4274(01)00504-5. View

10.

Farabollini F, Porrini S, Seta D, Bianchi F, Dessi-Fulgheri F . Effects of perinatal exposure to bisphenol A on sociosexual behavior of female and male rats. Environ Health Perspect. 2002; 110 Suppl 3:409-14. PMC: 1241191. DOI: 10.1289/ehp.02110s3409. View

11.

Quesada I, Fuentes E, Viso-Leon M, Soria B, Ripoll C, Nadal A . Low doses of the endocrine disruptor bisphenol-A and the native hormone 17beta-estradiol rapidly activate transcription factor CREB. FASEB J. 2002; 16(12):1671-3. DOI: 10.1096/fj.02-0313fje. View

12.

Sato K, Matsuki N, Ohno Y, Nakazawa K . Effects of 17beta-estradiol and xenoestrogens on the neuronal survival in an organotypic hippocampal culture. Neuroendocrinology. 2002; 76(4):223-34. DOI: 10.1159/000065948. View

13.

Moriyama K, Tagami T, Akamizu T, Usui T, Saijo M, Kanamoto N . Thyroid hormone action is disrupted by bisphenol A as an antagonist. J Clin Endocrinol Metab. 2002; 87(11):5185-90. DOI: 10.1210/jc.2002-020209. View

14.

Wetherill Y, Petre C, Monk K, Puga A, Knudsen K . The xenoestrogen bisphenol A induces inappropriate androgen receptor activation and mitogenesis in prostatic adenocarcinoma cells. Mol Cancer Ther. 2002; 1(7):515-24. View

15.

Silva A . Molecular and cellular cognitive studies of the role of synaptic plasticity in memory. J Neurobiol. 2002; 54(1):224-37. DOI: 10.1002/neu.10169. View

16.

Safe S, Pallaroni L, Yoon K, Gaido K, Ross S, McDonnell D . Problems for risk assessment of endocrine-active estrogenic compounds. Environ Health Perspect. 2003; 110 Suppl 6:925-9. PMC: 1241274. DOI: 10.1289/ehp.02110s6925. View

17.

Levin-Allerhand J, Lominska C, Wang J, Smith J . 17Alpha-estradiol and 17beta-estradiol treatments are effective in lowering cerebral amyloid-beta levels in AbetaPPSWE transgenic mice. J Alzheimers Dis. 2003; 4(6):449-57. DOI: 10.3233/jad-2002-4601. View

18.

Znamensky V, Akama K, McEwen B, Milner T . Estrogen levels regulate the subcellular distribution of phosphorylated Akt in hippocampal CA1 dendrites. J Neurosci. 2003; 23(6):2340-7. PMC: 6742003. View

19.

Gandy S . Estrogen and neurodegeneration. Neurochem Res. 2003; 28(7):1003-8. DOI: 10.1023/a:1023246921127. View

20.

Howdeshell K, Peterman P, Judy B, Taylor J, Orazio C, Ruhlen R . Bisphenol A is released from used polycarbonate animal cages into water at room temperature. Environ Health Perspect. 2003; 111(9):1180-7. PMC: 1241572. DOI: 10.1289/ehp.5993. View