Psychosocial stress enhances susceptibility to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity in C57BL/6N mice.

Abstract

Psychological stress is thought to be a risk factor for the onset or accelerate the progression of Parkinson's disease. The main aim of this study is to explore the causative effect of confrontational housing (CH), a paradigm developed as an animal model of psychosocial stress, in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. When mice were housed confrontationally for 24 h, they displayed increased anxiety like-behavior in the light/dark box test. Administration of MPTP after CH for 24 h caused severe damage of striatal dopaminergic neurons as indicated by decreases in dopamine transporter and tyrosine hydroxylase proteins and an increase of glial fibrillary acidic protein levels compared to CH alone. The dose of MPTP used this study slightly affected these protein levels in the striatum of control mice, but they did not significantly change. Our results indicate that the striatal dopaminergic neurons are vulnerable to environmental risk factors that presumably have neurotoxin-like properties under psychological stress condition.