Tuesday, May 24, 2011

Study Watch : IL-6 is increased in the cerebellum of the autistic brain and alters neural cell adhesion, migration and synapse formation

If you ever wondered how a dysregulated immune system could lead to the symptoms of autism, here is one possible answer for you.  A new study has added to the evidence that interleukin 6, a chemical messenger produced by and used by the immune system, can be abnormally high in the brains of some people with autism. More importantly, it showed that it is possible that these high levels of IL-6 can modify the physical functioning of the brain.

Or at least it can alter the physical properties of bits of mouse brains in petri dishes.  Replication of this exact study in human brains will have to wait until someone allows some researchers to play mad scientist with their brains...

Sorry, couldn't resist the bad joke.  But seriously, this is an interesting study and if you are interested in the immune system and how it could impact the functioning of the brain, it is worth reading.  The study is open access, so the entire text is freely available here.

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

Wei H, Zou H, Sheikh A, Malik M, Dobkin C, Brown T, Li X.

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.

PMID: 21595886
DOI: 10.1186/1742-2094-8-52

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