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Open Access Research

Alteration of astrocytes and Wnt/β-catenin signaling in the frontal cortex of autistic subjects

Fujiang Cao14, Ailan Yin1, Guang Wen2, Ashfaq M Sheikh1, Zujaja Tauqeer1, Mazhar Malik1, Amenah Nagori1, Michael Schirripa1, Frank Schirripa1, George Merz3, Shiqing Feng4, W Ted Brown3 and Xiaohong Li1*

Author Affiliations

1 Department of Neurochemistry, NY State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island New York, USA

2 Department of Developmental Neurobiology, NY State Institute for Basic Research in Developmental Disabilities, 10314, New York, NY, USA

3 Digital Microscopy, NY State Institute for Basic Research in Developmental Disabilities, 10314, New York, NY, USA

4 Department of Orthopaedics, General Hospital of Tianjin Medical Universtiy, Tianjin, China

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Journal of Neuroinflammation 2012, 9:223  doi:10.1186/1742-2094-9-223

Published: 21 September 2012

Abstract

Background

Autism is a neurodevelopmental disorder characterized by impairments in social interaction, verbal communication and repetitive behaviors. To date the etiology of this disorder is poorly understood. Studies suggest that astrocytes play critical roles in neural plasticity by detecting neuronal activity and modulating neuronal networks. Recently, a number of studies suggested that an abnormal function of glia/astrocytes may be involved in the development of autism. However, there is yet no direct evidence showing how astrocytes develop in the brain of autistic individuals.

Methods

Study subjects include brain tissue from autistic subjects, BTBR T + tfJ (BTBR) and Neuroligin (NL)-3 knock-down mice. Western blot analysis, Immunohistochemistry and confocal microscopy studies have been used to examine the density and morphology of astrocytes, as well as Wnt and β-catenin protein expression.

Results

In this study, we demonstrate that the astrocytes in autisitc subjects exhibit significantly reduced branching processes, total branching length and cell body sizes. We also detected an astrocytosis in the frontal cortex of autistic subjects. In addition, we found that the astrocytes in the brain of an NL3 knockdown mouse exhibited similar alterations to what we found in the autistic brain. Furthermore, we detected that both Wnt and β-catenin proteins are decreased in the frontal cortex of autistic subjects. Wnt/β-catenin pathway has been suggested to be involved in the regulation of astrocyte development.

Conclusions

Our findings imply that defects in astrocytes could impair neuronal plasticity and partially contribute to the development of autistic-like behaviors in both humans and mice. The alteration of Wnt/β-catenin pathway in the brain of autistic subjects may contribute to the changes of astrocytes.

Keywords:
Autism; Astrocytes; Morphology; Wnt/β-catenin pathway; Neural plasticity