Identification of dopamine- and serotonin-related genes modulated by bisphenol A in the prefrontal cortex of male rats

• We assessed neurotoxicity of BPA in relation to precortical DA and 5-HT systems.
• Perinatal BPA exposure affected gene transcription in juvenile and adult male rats.
• BPA reduced the transcripts of precortical DA receptors in juvenile rats.
• BPA produced permanent alterations in Gdnf transcript levels.
• BPA reduced Tph2 and increased Th transcription in adult rats.

There is concern that exposure of embryos and/or infants to bisphenol A (BPA) may lead to neurological and behavioral disorders with unknown prefrontal cortex (PFC) involvement. Critical PFC functions are modulated by dopamine (DA) and serotonin (5-HT) systems, whose alterations have been associated with psychopathologies that may appear in youth and/or adulthood. This study aims to determine in the PFC of male rats exposed to a low dose of BPA (10 μg kg−1 d−1) from gestational day 12 (GD12) to postnatal day 21 (PND21): (i) DA- and 5-HT-related genes modulated by BPA at the juvenile stage (PND21); (ii) reversible and irreversible transcriptional effects; (iii) long-term consequences (effects in adult rats, PND90). In juvenile rats, BPA altered significantly the transcription of 12 out of the 84 genes analyzed using PCR-array techniques. Interestingly, transcript levels of the neurotrophic factor Gdnf were decrease by BPA in both juvenile and adult rats. At adulthood, disruptions in genes encoding rate-limiting enzymes for DA and 5-HT synthesis emerged. Overall, the results indicate that early-life exposure to BPA has consequences on DA and 5-HT systems in both juvenile- and adult-life stages. Additionally, we reveal molecular targets that could provide the foundation for future BPA neurotoxicity studies.

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