Temporal Effects of Bisphenol A on Dopaminergic Neurons: An Experiment on Adult Rats



Masami Ishido*, 1, Yoshinori Masuo2
1 Center for Environmental Risk Research, National Institute for Environmental Studies, Japan
2 Toho University, Laboratory of Neuroscience, Department of Biology, Faculty of Science, Chiba, Japan


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© 2014 Ishido and Masuo

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Center for Environmental Risk Research, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan; Tel: +81-29(850)-2396; Fax: +81-29(850)-2870; E-mail:ishidou@nies.go.jp


Abstract

The vulnerability of developing brains to environmental chemicals has been reported. Here, we examined the temporal effects of bisphenol A on dopaminergic neurons. Exposure of 5-day-old rats to bisphenol A caused hyperactivity in juveniles, after which spontaneous motor activity leveled off at 8 weeks of age, when apoptotic cell death was still observed along with the loss of tyrosine hydroxylase immunoreactivity. Accumulation of α-synuclein, a pathological marker of neurodegeneration, was also detectable in the substantia nigra, but not in the cerebral cortex. In adult rats, acute toxicity following microinjection of bisphenol A (20 μg) caused degeneration of dopaminergic neurons, similar to that following administration of 6-hydroxydopamine (15 μg). Chronic exposure of adult rats to bisphenol A (3 mg/kg/day for 28 days) caused neurodegeneration in the substantia nigra. However, behavioral effects were not seen after either acute or chronic exposure of adult rats to bisphenol A.

Thus, the sensitivity of the central nervous system to bisphenol A was shown to be different at different life stages, confirming the greater vulnerability of the developing central nervous system.

Keywords: Bisphenol A, endocrine disruptors, neurodegeneration, vulnerability.