Abstract
Several neurological and behavioral dysfunctions have been reported in animals exposed to bisphenol A (BPA). However, little is known about the impact of adult exposure to BPA on brain physiopathology. Here, we focused on prefrontal cortex (PFC) of rats, because it is an important area for cognitive control, complex behaviors and is altered in many psychopathologies. Gamma-aminobutyric acid (GABA) and serotonin (5-HT) systems are essential for PFC function. Therefore, we examined the effects of adult exposure to BPA on 5α-Reductase (5α-R) and cytochrome P450 aromatase (P450arom), enzymes that synthesize GABAA receptor modulators, and tryptophan hydroxylase (Tph), the rate-limiting enzyme in 5-HT biosynthesis. To gain better understanding of BPA’s action in the adult PFC, 84 genes involved in neurotoxicity were also analysed. Adult male and female rats were subcutaneously injected for 4 days with 50 µg/kg/day, the current reference safe dose for BPA. mRNA and protein levels of 5α-R, P450arom and Tph were quantified by real-time RT-PCR and Western blot. Genes linked to neurotoxicity were analyzed by PCR-Array technology. Adult exposure to BPA increased both P450arom and Tph2 expression in PFC of male and female, but decreased 5α-R1 expression in female. Moreover, we identified 17 genes related to PFC functions such as synaptic plasticity and memory, as potential targets of BPA. Our results provided new insights on the molecular mechanisms underlying BPA action in the physiopathology of PFC, but also raise the question about the safety of short-term exposure to it in the adulthood.
Highlights
In recent years, considerable attention has been focused on endocrine-disrupting compounds and their impacts on the environment and human health, raising questions about their levels of exposure
The aim of the present study was to evaluate the effects of adult exposure to Bisphenol A (BPA) on 5a-R isozymes, P450arom and tryptophan hydroxylase (Tph) isozymes in the prefrontal cortex (PFC) of rats, at doses considered safe by the United States Environmental Protection Agency (EPA)
BPA treatment was randomly distributed across the phases of estrus, because we aimed to design our experiments in a way that reflects the exposure to this endocrine disruptor in real life, where the phase of the menstrual cycle in women is not taken into account when exposition occurs
Summary
Considerable attention has been focused on endocrine-disrupting compounds and their impacts on the environment and human health, raising questions about their levels of exposure. Numerous studies have shown that BPA is able to alter endocrine signalling pathways, leading to adverse biological effects [3,4,5,6]. Experiments with animals suggest that exposure to this compound may impair brain development, sexual differentiation, cognitive functions and behavior [7]. Most research has focused on the neurotoxic effects associated with perinatal exposure to BPA and the mechanism of action behind these neuro-developmental effects [9]. Recent works point out to adverse effects of BPA on adult brain [10,11], there is still limited toxicogenomic information on BPA-induced neurotoxicity during adult life
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