Journal of Autism and Developmental Disorders

, Volume 31, Issue 6, pp 529–535 | Cite as

Dysregulation of Reelin and Bcl-2 Proteins in Autistic Cerebellum

  • S. Hossein Fatemi
  • Joel M. Stary
  • Amy R. Halt
  • George R. Realmuto
Article

Abstract

Autism is a severe neurodevelopmental disorder with potential genetic and environmental causes. Cerebellar pathology including Purkinje cell atrophy has been demonstrated previously. We hypothesized that cell migration and apoptotic mechanisms may account for observed Purkinje cell abnormalities. Reelin is an important secretory glycoprotein responsible for normal layering of the brain. Bcl-2 is a regulatory protein responsible for control of programmed cell death in the brain. Autistic and normal control cerebellar corteces matched for age, sex, and post-mortem interval (PMI) were prepared for SDS-gel electrophoresis and Western blotting using specific anti-Reelin and anti-Bcl-2 antibodies. Quantification of Reelin bands showed 43%, 44%, and 44% reductions in autistic cerebellum (mean optical density ± SD per 30 μg protein 4.05 ± 4.0, 1.98 ± 2.0, 13.88 ± 11.9 for 410 kDa, 330 kDa, and 180 kDa bands, respectively; N = 5) compared with controls (mean optical density ± SD per 30 μg protein, 7.1 ± 1.6, 3.5 ± 1.0, 24.7 ± 5.0; N = 8, p < 0.0402 for 180 kDa band). Quantification of Bcl-2 levels showed a 34% to 51% reduction in autistic cerebellum (M ± SD per 75 μg protein 0.29 ± 0.08; N = 5) compared with controls (M ± SD per 75 μg protein 0.59 ± 0.31; N = 8, p < 0.0451). Measurement of β-actin (M ± SD for controls 7.3 ± 2.9; for autistics 6.77 ± 0.66) in the same homogenates did not differ significantly between groups. These results demonstrate for the first time that dysregulation of Reelin and Bcl-2 may be responsible for some of the brain structural and behavioral abnormalities observed in autism.

Cerebellum autism Reelin Bcl-2 

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Copyright information

© Plenum Publishing Corporation 2001

Authors and Affiliations

  • S. Hossein Fatemi
    • 1
    • 2
    • 3
  • Joel M. Stary
    • 1
  • Amy R. Halt
    • 1
  • George R. Realmuto
    • 2
    • 4
  1. 1.Department of PsychiatryUniversity of Minnesota Medical SchoolMinneapolis
  2. 2.Department of NeuroscienceUniversity of Minnesota Medical SchoolMinneapolis
  3. 3.Division of Neuroscience ResearchUSA
  4. 4.Division of Child PsychiatryUSA

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