Alteration of astrocytes and Wnt/beta-catenin signaling in the frontal cortex of autistic subjects
Ashfaq Sheikh, Guang Wen, Fujiang Cao, Ailan Yin, Mazhar Malik, Zujaja Tauqeer, Amenah Nagori, Michael Schirripa, Frank Schirripa, George Merz, Ted Brown and Xiaohong Li
Journal of Neuroinflammation 2012, 9:223 doi:10.1186/1742-2094-9-223
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.
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 be used to examine the density and morphology of astrocytes, as well as Wnt and beta-catenin protein expression.
In this study, we demonstrate that the astrocytes in autisitcsubjects 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 beta-catenin proteins are decreased in the frontal cortex of autistic subjects. Wnt/beta-catenin pathway has been suggested to be involved in the regulation of astrocyte development.
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/beta-catenin pathway in the brain of autistic subjects may contribute to the changes of astrocytes.