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

J Neuroinflammation. 2011 May 19;8:52. doi: 10.1186/1742-2094-8-52.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autistic Disorder / immunology
  • Autistic Disorder / physiopathology*
  • Cell Adhesion / physiology*
  • Cell Movement / physiology*
  • Cerebellum / cytology
  • Cerebellum / metabolism*
  • Child
  • Child, Preschool
  • Dendritic Spines / metabolism
  • Dendritic Spines / ultrastructure
  • Gene Transfer Techniques
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Neurons / cytology
  • Neurons / physiology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Synapses / physiology*
  • Synapses / ultrastructure

Substances

  • Interleukin-6
  • Recombinant Fusion Proteins