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.