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Publication : MPTP susceptibility in the mouse: behavioral, neurochemical, and histological analysis of gender and strain differences.

First Author  Sedelis M Year  2000
Journal  Behav Genet Volume  30
Issue  3 Pages  171-82
PubMed ID  11105391 Mgi Jnum  J:65697
Mgi Id  MGI:1927059 Doi  10.1023/a:1001958023096
Citation  Sedelis M, et al. (2000) MPTP susceptibility in the mouse: behavioral, neurochemical, and histological analysis of gender and strain differences. Behav Genet 30(3):171-82
abstractText  To investigate the impact of strain and sex in the l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of Parkinson's disease, C57BL/6 and 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, neostriatal and ventral striatal monoamine contents were determined, and the numbers of tyrosine hydroxylase-immunostained cells were counted in the substantia nigra and ventral tegmental area. Open-field testing showed that locomotor activity was drastically reduced as an acute effect of MPTP in both strains; however, subsequent recovery to control levels was faster in BALB/c mice than in C57BL/6. Nest building also indicated strain-dependent effects, since it was delayed only in C57BL/6 mice treated with MPTP. The other tests (grip test, pole test, rotarod, elevated plus-maze), although partly sensitive for over-all strain or gender differences, turned out not to be useful to compare MPTP effects in these two strains. Neurochemically, MPTP led to more severe neostriatal dopamine depletions in C57BL/6 (-85%) than in BALB/c mice (-58%). Histologically, a loss of tyrosine hydroxylase immunoreactivity (-25%) was observed only in the substantia nigra of C57BL/6 animals. Thus, our analysis consistently showed that the C57BL/6 mouse strain is more susceptible to MPTP than the BALB/c strain. Sex differences in MPTP sensitivity were not observed in our mice. The implications of these findings for the search for genes related to susceptibility to neurodegeneration are discussed.
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