Autism is a neurodevelopmental disorder with genetic and environmental etiologies. Neurohistologic findings have shown Purkinje cell depletion and atrophy in the cerebellum of autistic subjects. We hypothesized that apoptotic mechanisms might explain these Purkinje cell findings. Bcl-2 is a potent antiapoptotic regulatory protein, which is reduced in schizophrenic brains. Autistic and normal control cerebellar cortices matched for age, sex and PMI were prepared for SDS-gel electrophoresis and Western blotting using specific anti-Bcl-2 antibodies. Quantification of Bcl-2 showed a significant 34-51% reduction in autistic cerebellum (mean (± s.d.) optical density/75 μg 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 βtubulin (controls 49.8 ± 6.7; autistics 36.2 ± 18.2), or β-actin (controls 7.3 ± 2.7; autistics 6.77 ± 0.66) in the same homogenates did not differ significantly between groups. These results indicate for the first time that autistic cerebellum may be vulnerable to pro-apoptotic stimuli and to neuronal atrophy as a consequence of decreased Bcl-2 levels.
- Neuron-specific β-tubulin
- Western blotting