Fig. 3.

Loss of p53 in gene-targeted mice attenuates MPTP-induced SNpc DA apoptotic cell death. (a and b) At the peak of MPTP-induced mitochondria-dependent apoptotic cell death (4 days after the last MPTP injection), cytochrome c release and caspase-3 activation are reduced in ventral midbrain cytosolic fractions of p53-deficient mice. (c) The number of MPTP-induced SNpc apoptotic neurons is decreased in the ventral midbrain of p53-deficient mice compared with similarly treated wild-type mice. Morphological criteria to identify apoptotic cells included shrinkage of the cell body, chromatin condensation, and the presence of distinct, round, well defined chromatin clumps, demonstrated on thionin staining, as in ref. 8. (d) p53-deficient mice exhibit a significant protection against MPTP-induced SNpc DA cell death, as determined by assessing the number of SNpc DA neurons at 21 days after the last MPTP injection. ∗, P < 0.05 compared with saline-injected mice; #, P < 0.05 compared with MPTP-injected wild-type mice.