IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation

• Main Authors: Dobkin Carl, Malik Mazhar, Sheikh Ashfaq M, Zou Hua, Wei Hongen, Brown W Ted, Li Xiaohong
• Format: Article
• Language: English
• Published: BMC 2011-05-01
• Series: Journal of Neuroinflammation
• Subjects: Autism; cytokines; synapse development; neural adhesion and migration; apoptosis; inflammation
• Online Access: http://www.jneuroinflammation.com/content/8/1/52

<p>Abstract</p> <p>Background</p> <p>Although the cellular mechanisms responsible for the pathogenesis of autism are not understood, a growing number of studies have suggested that localized inflammation of the central nervous system (CNS) may contribute to the development of autism. Recent evidence shows that IL-6 has a crucial role in the development and plasticity of CNS.</p> <p>Methods</p> <p>Immunohistochemistry studies were employed to detect the IL-6 expression in the cerebellum of study subjects. <it>In vitro </it>adenoviral gene delivery approach was used to over-express IL-6 in cultured cerebellar granule cells. Cell adhesion and migration assays, DiI labeling, TO-PRO-3 staining and immunofluorescence were used to examine cell adhesion and migration, dendritic spine morphology, cell apoptosis and synaptic protein expression respectively.</p> <p>Results</p> <p>In this study, we found that IL-6 was significantly increased in the cerebellum of autistic subjects. We investigated how IL-6 affects neural cell development and function by transfecting cultured mouse cerebellar granule cells with an IL-6 viral expression vector. We demonstrated that IL-6 over-expression in granule cells caused impairments in granule cell adhesion and migration but had little effect on the formation of dendritic spines or granule cell apoptosis. However, IL-6 over-expression stimulated the formation of granule cell excitatory synapses, without affecting inhibitory synapses.</p> <p>Conclusions</p> <p>Our results provide further evidence that aberrant IL-6 may be associated with autism. In addition, our results suggest that the elevated IL-6 in the autistic brain could alter neural cell adhesion, migration and also cause an imbalance of excitatory and inhibitory circuits. Thus, increased IL-6 expression may be partially responsible for the pathogenesis of autism.</p>