Glia cell number modulates sensitivity to MPTP in mice.

Free radical damage has been shown to play a significant role in the pathogenesis of a number of neurodegenerative diseases including Parkinson's disease. One model of experimental parkinsonism is the loss of substantia nigra cells following administration of MPTP. Previously, it has been shown that a number of inbred strains of mice have differential responses to this toxin, and this difference is dependent on glial cells. In this study, the number of glial cells in the substantia nigra pars compacta of C57Bl/6J (MPTP-sensitive) and Swiss Webster (MPTP-resistant) strains of mice was examined. The C57Bl/6J mice have an approximately 50% lower number of GFAP+ and S-100beta glial cells than the Swiss Webster mice. C57Bl/6J mice have a 25% increased number of resident nonactivated microglial cells. To determine whether this difference in cell number has functional significance, we used an in vitro SN culture system that allowed us to manipulate the number of glial cells. When C57Bl/6 neurons were grown on a glial mat plated with twice the number of cells, we were able to rescue the MPTP-sensitive neurons from toxin-induced cell death. This suggests that the number of glial cells in the SNpc may be an important factor in the survival of dopaminergic neurons following exposure to xenobiotics.