MPTP susceptibility in the mouse: Behavioral, neurochemical, and histological analysis of gender and strain differences

To investigate the impact of strain and sex in the 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) animal model of Parkinson's disease, C57BL/6 an d BALB/c mice were treated with either systemic MPTP-HCl (4 x 15 mg/kg) or saline and were examined in a number of behavioral tests. Furthermore, neos triatal and ventral striatal monoamine contents were determined, and the nu mbers of tyrosine hydroxylase-immunostained cells were counted in the subst antia nigra and ventral tegmental area. Open-field testing showed that loco motor activity was drastically reduced as an acute effect of MPTP in both s trains; however, subsequent recovery to control levels was faster in BALB/c mice than in C57BL/6. Nest building also indicated strain-dependent effect s, since it was delayed only in C57BL/6 mice treated with MPTP. The other t ests (grip test, pole test, rotarod, elevated plus-maze), although partly s ensitive for overall strain or gender differences, turned out not to be use ful to compare MPTP effects in these two strains. Neurochemically, MPTP led to more severe neostriatal dopamine depletions in C57BL/6 (-85%) than in B ALB/c mice (-58%). Histologically, a loss of tyrosine hydroxylase immunorea ctivity (-25%) was observed only in the substantia nigra of C57BL/6 animals . Thus, our analysis consistently showed that the C57BL/6 mouse strain is m ore susceptible to MPTP than the BALB/c strain. Sex differences in MPTP sen sitivity were not observed in our mice. The implications of these findings for the search for genes related to susceptibility to neurodegeneration are discussed.