Autism is a neurodevelopmental disorder characterized by impairments in social interaction, verbal communication and repetitive behaviors. Recent studies suggest that one of the major pathways to the pathogenesis of autism is reduced cell migration. The cadherin family of transmembrane glycoproteins plays an essential role in the initiation and stabilization of cell–cell contacts, thus significantly involved in the regulation of cell adhesion and migration. Classical cadherins, including E-cadherin, bind to either β-catenin or γ-catenin (plakoglobin), which links this complex to α-catenin. Without α-catenin, cells do not associate tightly with each other despite the expression of cadherins.
Objectives: The aim of this study is to determine whether cadherins and catenins are altered in the autistic brain
Methods:
Frozen human brain tissues of six autistic subjects (mean age 8.3 ± 3.8 years) and six age-matched normal subjects (mean age 8 ± 3.7 years) were obtained from the NICHD Brain and Tissue Bank for Developmental Disorders. Donors with autism fit the diagnostic criteria of the Diagnostic and Statistical Manual-IV, as confirmed by the Autism Diagnostic Interview-Revised. In this study, Western Blot Analyses and Immunohistochemistry studies were used to detect the protein expression levels of E-cadherin, P-cadherin, α-catenin and β-catenin. Immunohistochemistry studies have also been used to examine the morphology of neural glial cells.
Results:
With western blot analysis, we show that the expression of α-catenin is significantly increased in both frontal cortex and cerebellum of autistic brain as compared with the age-matched controls. To further confirm this results, we carried out immunohistochemistry studies. We detected that the increased α-catenin expression is restricted in the glial cells of autistic brain. We did not detect significant differences in the expression of E-cadherin and P-cadherin between autistic and control brains. The determination of β-catenin is not yet completed. Since we found that α-catenin expression was significantly increased in the glial cells of autistic brain, we further examined whether glial cells in autistic brain are different from the controls. Using anti-GFAP (glial fibrillary acidic protein) antibody, our pilot study showed that the branching of glial cells (astrocytes) in autistic brain is significantly decreased as compared with the controls.
Conclusions:
Our findings suggest that the up-regulation of α-catenin in the glial cells of autistic brain could affect the structure and function of glial cells, which may contribute to the pathogenesis of autism
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