DIFFERENCES IN NIGRAL NEURON NUMBER AND SENSITIVITY TO 1-METHYL-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 reductio ns 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 determ ine the possible reasons for this difference in MPTP sensitivity betwe en these two mouse strains, we have compared both the organization and the number of substantia nigra (SN) neurons, the primary target of MP TP, in C57/bl and in CD-1 mice using immunostaining for tyrosine hydro xylase (TH) and calbindin-D-28k (calbindin). In saline-injected animal s, there is a significantly lower number of SN TH-positive and calbind in-positive neurons in C57/bl than CD-1 mice; no significant differenc es 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 i n the numbers of SN calbindin-positive neurons in either strain. The p resent study shows that C57/bl mice which have fewer SN TH-positive ne urons are more sensitive to MPTP-induced toxicity than CD-1 mice. This observation suggests a possible inverse relationship between SN TH-po sitive neuron number and MPTP sensitivity. If correct, this hypothesis may be of major importance for Parkinson's disease since it is sugges ted that individuals at risk of developing this neurodegenerative diso rder may have lower numbers of SN TH-positive neurons to start with. T he present study also shows that SN calbindin-positive neuron numbers does not account for the differential sensitivity to MPTP between thes e two mouse strains. (C) 1994 Academic Press, Inc.