Reduction in anti-apoptotic protein Bcl-2 in autistic cerebellum.
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 anti-apoptotic 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 microg 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 (controls 49.8 +/- 6.7; autistics 36.2 +/- 18.2), or beta-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.
Fatemi
S H
SH
Department of Psychiatry, University of Minnesota Medical School, Minneapolis 55455, USA.
Halt
A R
AR
Stary
J M
JM
Realmuto
G M
GM
Jalali-Mousavi
M
M
D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D001321:Autistic Disorder / Q000378:metabolism*; D015153:Blotting, Western; D001923:Brain Chemistry; D002525:Cerebellar Cortex / Q000737:chemistry / Q000378:metabolism; D002531:Cerebellum / Q000737:chemistry / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*
D009419:Nerve Tissue Proteins; D019253:Proto-Oncogene Proteins c-bcl-2