Differences in Nigral Neuron Number and Sensitivity to 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine in C57/bl and CD-1 Mice

The present study demonstrates that the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes significantly greater reductions in striatal dopamine levels in C57/bl mice than in CD-1 mice, thus confirming a greater sensitivity of the C57/bl mice to MPTP. To determine the possible reasons for this difference in MPTP sensitivity between these two mouse strains, we have compared both the organization and the number of substantia nigra (SN) neurons, the primary target of MPTP, in C57/bl and in CD-1 mice using immunostaining for tyrosine hydroxylase (TH) and calbindin-D28k (calbindin). In saline-injected animals, there is a significantly lower number of SN TH-positive and calbindin-positive neurons in C57/bl than CD-1 mice; no significant differences in the numbers of these neurons are found in the ventral tegmental area between the two strains. In MPTP-injected animals, the reductions in SN TH-positive neurons are significantly greater in C57/bl than in CD-1 mice. In contrast, MPTP does not cause any significant changes in the numbers of SN calbindin-positive neurons in either strain. The present study shows that C57/bl mice which have fewer SN TH-positive neurons are more sensitive to MPTP-induced toxicity than CD-1 mice. This observation suggests a possible inverse relationship between SN TH-positive neuron number and MPTP sensitivity. If correct, this hypothesis may be of major importance for Parkinson's disease since it is suggested that individuals at risk of developing this neurodegenerative disorder may have lower numbers of SN TH-positive neurons to start with. The present study also shows that SN calbindin-positive neurons are spared following MPTP administration. However, the observed difference in SN calbindin-positive neuron numbers does not account for the differential sensitivity to MPTP between these two mouse strains.