Abstract
We have been studying the mechanisms underlying motor hyperactivity caused by the deficit in dopaminergic neurons. In the present study, we examined the effects of endocrine disruptors (EDs) on the central nervous system. EDs are mainly derived from industrial products and are detected in the human umbilical cord and cord serum. Male Wistar rats received intracisternal injection of EDs at 5 days of age. Some phenols and phthalates caused a significant increase in spontaneous motor activity in both the dark and light phases at 4 weeks of age, while 6-hydroxydopamine (6-OHDA) induced hyperactivity in the dark phase. Bisphenol A, octylphenol and p-nonylphenol diminished tyrosine hydroxylase (TH) immunoreactivity in the midbrain. Gene expression profiles determined by DNA array in the midbrain and striatum varied with EDs and differed from that of 6-OHDA. Neonatal treatment with EDs may affect several factors including dopaminergic neurons. We further examined the effects of EDs injected into the unilateral substantia nigra in 9-week-old rats. Circling behavior was found towards the side ipsilateral to ED injection after methamphetamine treatment, and TH immunoreactivity was attenuated on the injection side. These results suggest that neonatal exposure to EDs may provide an animal model of developmental disorders, such as attention-deficit hyperactivity disorder that show clinical variation. Treatment with EDs in adulthood may also generate an animal model of neurodegenerative disorders, such as Parkinson's disease. [Jpn J Physiol 54 Suppl:S250 (2004)]
