Reduction in anti-apoptotic protein Bcl-2 in autistic cerebellum

Autism is a neurodevelopmental disorder with genetic and environmental etio logies. Neurohistologic findings have shown Purkinje cell depletion and atr ophy in the cerebellum of autistic subjects. We hypothesized that apoptotic mechanisms might explain these Purkinje cell findings. Bcl-2 is a potent a nti-apoptotic regulatory protein, which is reduced in schizophrenic brains. Autistic and normal control cerebellar cortices matched for age, sex and P MI were prepared for SDS-gel electrophoresis and Western blotting using spe cific anti-Bcl-2 antibodies. Quantification of Bcl-2 showed a significant 3 4-51% reduction in autistic cerebellum (mean (+/- s.d.) optical density/75 mug protein 0.290 +/- 0.08, n = 5) compared with controls (0.595 +/- 0.31, n = 8; p < 0.04); levels of neuronal-specific class III (<beta>-tubulin (co ntrols 49.8 +/- 6.7; autistics 36.2 +/- 18.2), or (beta -actin (controls 7. 3 +/- 12.7; autistics 6.77 +/- 0.66) in the same homogenates did not differ significantly between groups. These results indicate for the first time th at autistic cerebellum may be vulnerable to pro-apoptotic stimuli and to ne uronal atrophy as a consequence of decreased Bcl-2 levels. NeuroReport 12:9 29-933 (C) 2001 Lippincott Williams & Wilkins.