title: IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Immunohistochemistry studies were employed to detect the IL-6 expression in the cerebellum of study subjects. In vitro 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Neurochemistry, NY State Institute for Basic Research in Developmental Disabilities, New York, USA.
authors: Hongen
authors: H
authors: Wei
authors: Hua
authors: H
authors: Zou
authors: Ashfaq M
authors: AM
authors: Sheikh
authors: Mazhar
authors: M
authors: Malik
authors: Carl
authors: C
authors: Dobkin
authors: W Ted
authors: WT
authors: Brown
authors: Xiaohong
authors: X
authors: Li
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