Fig. 4.
Role of Bim in MPTP-induced SNpc DA neurodegeneration. (a) Ventral midbrain bim mRNA expression is induced in a time-dependent manner after MPTP intoxication, peaking at 24 h post-MPTP. (b) At its peak, MPTP-induced bim mRNA up-regulation is prevented in JNK-3-deficient mice. (c) At the peak of MPTP-induced bim mRNA up-regulation, mitochondrial BimEL protein levels are markedly increased in the ventral midbrain. (d) Loss of Bim in gene-targeted mice significantly attenuates MPTP-induced Bax mitochondrial translocation (Left) and cytochrome c release (Right), as assessed by Western blot analysis of mitochondrial and cytosolic fractions from ventral midbrain, respectively. (e and f) Bim-deficient mice exhibit a significant reduction in the number of MPTP-induced SNpc apoptotic neurons (e) and a significant protection from MPTP-induced SNpc DA cell death (f). ∗, P < 0.05 compared with saline-injected mice; #, P < 0.05 compared with MPTP-injected wild-type mice.