title: Dynamic changes in dopaminergic neurotransmission induced by a low concentration of bisphenol-A in neurones and astrocytes.
abstract: One of the most common chemicals that behaves as an endocrine disruptor is the compound 4,4'-isopronylidenediphenol, called bisphenol-A (BPA). We previously reported that prenatal and postnatal exposure to BPA potentiated central dopaminergic neurotransmission, resulting in supersensitivity to psychostimulant-induced pharmacological actions. Many recent findings have supported the idea that astrocytes, which are a subpopulation of glial cells, play a critical role in neuronal transmission in the central nervous system. The present study aimed to investigate the role of neurone-astrocyte communication in the enhancement of dopaminergic neurotransmission induced by BPA. We found that treatment of mouse purified astrocytes and neurone/glia cocultures with BPA in vitro caused the activation of astrocytes, as detected by a stellate morphology and an increase in levels of glial fibrillary acidic protein. A low concentration of BPA significantly enhanced the Ca2+ responses to dopamine in both neurones and astrocytes. Furthermore, a high concentration of BPA markedly induced the activation of caspase-3, which is a marker of neuronal apoptotic cell death in mouse midbrain neurone/glia cocultures. By contrast, treatment with 17beta-oestradiol (E2) had no such effects. Prenatal and neonatal exposure to BPA led to an enhancement of the dopamine-dependent rewarding effect induced by morphine. These findings provide evidence that BPA alters dopamine responsiveness in neurones and astrocytes and that, at least in part, it may contribute to potentiate the development of psychological dependence on drugs of abuse.
authors: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors: M
authors: M
authors: Miyatake
authors: K
authors: K
authors: Miyagawa
authors: K
authors: K
authors: Mizuo
authors: M
authors: M
authors: Narita
authors: T
authors: T
authors: Suzuki