Temporal Effects of Bisphenol A on Dopaminergic Neurons: An Experiment on Adult Rats

The vulnerability of developing brains to environmental chemicals has been reported. Here, we examined the temporal effects of bisphenol A on dopaminergic neurons. Exposure of 5-day-old rats to bisphenol A caused hyperactivity in juveniles, after which spontaneous motor activity leveled off at 8 weeks of age, when apoptotic cell death was still observed along with the loss of tyrosine hydroxylase immunoreactivity. Accumulation of α-synuclein, a pathological marker of neurodegeneration, was also detectable in the substantia nigra, but not in the cerebral cortex. In adult rats, acute toxicity following microinjection of bisphenol A (20 μg) caused degeneration of dopaminergic neurons, similar to that following administration of 6-hydroxydopamine (15 μg). Chronic exposure of adult rats to bisphenol A (3 mg/kg/day for 28 days) caused neurodegeneration in the substantia nigra. However, behavioral effects were not seen after either acute or chronic exposure of adult rats to bisphenol A. Thus, the sensitivity of the central nervous system to bisphenol A was shown to be different at different life stages, confirming the greater vulnerability of the developing central nervous system.