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ToxSci Advance Access published online on October 12, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfj012
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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 July 27, 2005
Accepted September 29, 2005

Neurotoxicology

The Endocrine Disruptor Atrazine Accounts for a Dimorphic Somatostatinergic Neuronal Expression Pattern in Mice

G. Giusi 1, R.M. Facciolo 1, M. Canonaco 1*, E. Alleva 2, V. Belloni 3, F. Dessi'-Fulgheri 3, and D. Santucci 2

1 Comparative Neuroanatomy Laboratory, Dept of Ecology, University of Calabria, 87036 Cosenza-Italy
2 Section of Behavioural Neurosciences, Dept of Cellular Biology and Neuroscience-Istituto Superiore di Sanità, 00161 Roma- Italy
3 Dept. of Animal Biology, University of Firenze, 50100 Firenze, Italy

* To whom correspondence should be addressed.
M. Canonaco, E-mail: canonaco{at}unical.it


  Abstract

It has now been established that a large number of man-made and natural chemicals are capable of interfering with the action of natural hormones. In this category "endocrine disruptors" such as the herbicide atrazine provided, when administered ecological low doses (1-100 µg/Kg/d) from gestational day 14 to postnatal day 21, a clear dimorphic neurodegenerative pattern in some brain areas of the domestic mouse (Mus musculus). Indeed, the high concentration (100 µg/Kg/d) with respect to the low (1 µg/Kg/d) induced relevant neuronal damages in extra-hypothalamic sites such as cortical and striatal areas of both sexes while marked alterations in other areas including hippocampal plus hypothalamic nuclei were mostly typical of the female. At the neuronal level, the neuropeptide somatostatin, specific for the secretion of growth hormone, seemed to be a major target of atrazine effects as demonstrated by evident subtype2,3,5 receptor mRNA differences of this neuropeptide, at least for the first two subtypes. In particular, a very strong (p <0.001) up-regulation of subtype2 expressing neurons was detected in female hypothalamic areas and namely the suprachiasmatic nucleus whereas a similar down-regulatory trend was reported for some extra-hypothalamic areas such as the striatum. Interestingly, very strong up- and down-regulatory actions were instead detected for neurons expressing subtype3 in male hypothalamic and amygdalar regions and in cortical and hippocampal areas, respectively. Overall, it appears that these first neurotoxicological effects of atrazine are very likely linked to dimorphic expression patterns of specific somatostatin subtypes in discrete but key hypothalamic and extra-hypothalamic areas of Mus musculus.

Keywords: atrazine; herbicide; dimorphism; somatostatinergic receptor subtypes; mice.
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