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ToxSci Advance Access published online on September 14, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi322
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received June 6, 2005
Accepted September 8, 2005

Neurotoxicology

Neurobiological Effects of Bisphenol A may be Mediated by Somatostatin Subtype3 Receptors in Some Regions of the Developing Rat Brain

Rosa Maria Facciolo 1*, Maria Madeo 2, Raffaella Alò 2, Marcello Canonaco 2, and Francesco Dessì-Fulgheri 3

1 Comparative Neuroanatomy Laboratory of Ecology Department, University of Calabria, 87030 Arcavata di Rende-Cosenza, Italy; Animal Biology Department, University of Firenze, 50100 Firenze, Italy
2 Comparative Neuroanatomy Laboratory of Ecology Department, University of Calabria, 87030 Arcavata di Rende-Cosenza, Italy
3 Animal Biology Department, University of Firenze, 50100 Firenze, Italy

* To whom correspondence should be addressed.
Rosa Maria Facciolo, E-mail: rm.facciolo{at}unical.it


  Abstract

Considerable attention has been focused on environmental disruptors such as the xenoestrogen bisphenol A that influences reproductive, developmental and cognitive activities through its interaction with specific neuromediating systems in an estrogen-like fashion. In the present study, the effects of this xenoestrogen proved to be preferentially directed towards hypothalamic and extra-hypothalamic somatostatin receptor subtype3 which displayed by a higher binding affinity of its specific nonpeptide agonist (L-796-778) than that of L-779-976 (subtype2). A first type of action consisted in a very strong (p < 0.001) decrease of somatostatin receptor subtype3 mRNA levels in the layer V of the frontoparietal cortex of adult rats (Sprague Dawley) following transplacental and lactational exposure of bisphenol A (400 µg/kg/day) with respect to those treated with only vehicle. In a similar manner, such a treatment was responsible, this time in 7 days old rats, for a very strong reduction and strong (p < 0.01) increase of the subtype3 mRNA levels in the hypothalamic periventricular and ventromedial nuclei, respectively. Moreover, even greater up- and down-regulated activities were reported when subtype3 mRNA levels were determined in the presence of receptor agonists that are specific for distinct {alpha} GABAA receptor subunits ({alpha}1,5). The predominant effects of bisphenol A on somatostatin receptor subtype3 mRNA levels occurring in an {alpha} GABAA subunit-dependent manner tend to suggest the early modulatory importance of this environmental disruptor on cross-talking mechanisms that are implicated in the plasticity of neural circuits with consequential influence on neuroendocrine/socio-sexual behaviors.

Keywords: nonpeptide agonists; GABAA receptor; xenoestrogens; cortex; hippocampus; hypothalamus.
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