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

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, when administered at ecological low doses (1 or 100 microg/kg per day) from gestational day 14 to postnatal day 21, provided a clear dimorphic neurodegenerative pattern in some brain areas of the domestic mouse (Mus musculus). Indeed, the high concentration (100 microg/kg per day) with respect to the low concentration (1 microg/kg per day) induced relevant neuronal damage in extrahypothalamic sites, such as the cortical and striatal areas in both sexes. Marked alterations in other areas, including the hippocampal and 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) upregulation of subtype2 expressing neurons was detected in female hypothalamic areas, specifically the suprachiasmatic nucleus, whereas a similar downregulatory trend was reported for some extrahypothalamic areas such as the striatum. Interestingly, very strong upregulatory and downregulatory actions were detected for neurons expressing subtype3 in male hypothalamic and amygdalar regions and in the 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 extrahypothalamic areas of Mus musculus.

WITHDRAWN: Gestational and lactational exposure to atrazine affects behavior and cognitive functions in Sprague-Dawley rats

“…Indeed, Belloni et al indicated that gestational and postnatal exposure to ATR altered motor activity in juvenile offspring and led to extensive neurodegenerative alterations in the cortex, striatum, hippocampus, and hypothalamus in adulthood [13,16]. This suggests that the developing nervous system may be sensitive to ATR, particularly in the early neural developmental stage.…”

Disposition of the Herbicide 2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine (Atrazine) and Its Major Metabolites in Mice: A Liquid Chromatography/Mass Spectrometry Analysis of Urine, Plasma, and Tissue Levels

“…Although data on health effects of ATR in humans are not complete, an increasing number of animal studies report that ATR exposure causes reproductive, developmental, and immunological alterations in laboratory rodents (Cooper et al, 1996Narotsky et al, 2001;Pruett et al, 2003;Filipov et al, 2005;Giusi et al, 2006;Rowe et al, 2006). The brain is another potential target organ for ATR as several in vitro and in vivo studies have suggested that excessive exposure to ATR may be neurotoxic (Das et al, 2000(Das et al, , 2001Rodriguez et al, 2005;Giusi et al, 2006;Coban and Filipov, 2007).…”

“…The brain is another potential target organ for ATR as several in vitro and in vivo studies have suggested that excessive exposure to ATR may be neurotoxic (Das et al, 2000(Das et al, , 2001Rodriguez et al, 2005;Giusi et al, 2006;Coban and Filipov, 2007). Most of the above-mentioned studies have been performed in rats (Cooper et al, 1996Narotsky et al, 2001;Rodriguez et al, 2005).…”

“…Most of the above-mentioned studies have been performed in rats (Cooper et al, 1996Narotsky et al, 2001;Rodriguez et al, 2005). However, mice are increasingly used in toxicology research, and the number of studies using mice for the assessment of potential adverse consequences of ATR exposure is increasing (National Toxicology Program, 1994;Pruett et al, 2003;Filipov et al, 2005;Giusi et al, 2006;Rowe et al, 2006;Coban and Filipov, 2007).…”

Herbicides and the Risk of Neurodegenerative Disease

“…Atrazine treatment reduced numbers of tyrosine hydroxylase immunoreactive neurons in the substantia nigra pars compacta and the ventral tegmental area (Coban & Filipov, 2007;Rodriguez et al, 2005), indicating that it is neurotoxic to dopaminergic neurons. Atrazine also caused general neurodegeneration in the hippocampus of the female mouse (Giusi et al, 2006). In vivo microdialysis experiments further showed that dopamine release in the striatum is reduced as a consequence of an acute exposure to atrazine (Rodríguez et al, 2005).…”