Strain-dependent susceptibility to MPTP and MPP+-induced parkinsonism is determined by glia

Parkinson's disease (PD) is a debilitating neurological disorder that strik es approximately 2% of people over age 50. Current hypotheses propose that the cause of PD is multifactorial, involving environmental agents and genet ic predisposition. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) indu ces parkinsonism in many species, including humans and shows strain specifi city in mice. The mechanism of strain specificity, however, remains unknown . Using novel chimeric murine substantia nigra cultures, we demonstrate tha t sensitivity to MPTP is conferred by glia and that it does not involve the MAO-B conversion of MPTP to MPP+. C57Bl/6J dopaminergic neurons exposed to MPP+ demonstrated a 39% loss when cultured on C57Bl/6J glia compared with 17% neuron loss when cultured on resistant SWR/J glia. Similarly, SWR/J neu rons exposed to MPP+ demonstrated a 4% loss when cultured on SWR/J glia, bu t a 14% loss when cultured on sensitive C57Bl/6J glia. The identification o f glia as the critical cell type in the genesis of experimental Parkinsonis m provides a target for the development of new anti-parkinsonian therapies. GLIA 34:73-80, 2001. (C) 2001 Wiley-Liss, Inc.