Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors

• Published in: Biochimica et biophysica acta Vol. 1822; no. 6; pp. 831 - 842
• Main Authors: Wei, Hongen, Chadman, Kathryn K., McCloskey, Daniel P., Sheikh, Ashfaq M., Malik, Mazhar, Brown, W. Ted, Li, Xiaohong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2012
• Subjects: Animals; Anxiety; Autism; Autistic Disorder - genetics; Autistic Disorder - immunology; Autistic Disorder - pathology; Autistic-like behavior; Brain - immunology; Brain - metabolism; Brain - ultrastructure; Cognition; Cytokine; Dendritic Spines - immunology; Dendritic Spines - metabolism; Dendritic Spines - ultrastructure; Excitatory Postsynaptic Potentials; Genetic Vectors; Green Fluorescent Proteins - genetics; IL-6; Inhibitory Postsynaptic Potentials; Interleukin-6 - genetics; Interleukin-6 - metabolism; Mice; Mice, Transgenic; Neuronal Plasticity; Neurons - physiology; Neurons - ultrastructure; Synapse development; Synaptic transmission; Synaptic Transmission - genetics; Synaptic Transmission - immunology; Autism; Autistic-like behavior; Synaptic transmission; IL-6; Cytokine; Synapse development
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/j.bbadis.2012.01.011

Abnormal immune responses have been reported to be associated with autism. A number of studies showed that cytokines were increased in the blood, brain, and cerebrospinal fluid of autistic subjects. Elevated IL-6 in autistic brain has been a consistent finding. However, the mechanisms by which IL-6 may be involved in the pathogenesis of autism are not well understood. Here we show that mice with elevated IL-6 in the brain display many autistic features, including impaired cognitive abilities, deficits in learning, abnormal anxiety traits and habituations, as well as decreased social interactions. IL-6 elevation caused alterations in excitatory and inhibitory synaptic formations and disrupted the balance of excitatory/inhibitory synaptic transmissions. IL-6 elevation also resulted in an abnormal change in the shape, length and distributing pattern of dendritic spines. These findings suggest that IL-6 elevation in the brain could mediate autistic-like behaviors, possibly through the imbalances of neural circuitry and impairments of synaptic plasticity. ►Mice with elevated IL-6 in the brain display many autistic features. ►IL-6 elevation caused alterations in excitatory and inhibitory synaptic formations. ►IL-6 elevation disrupted the balance of excitatory/inhibitory synaptic transmissions. ►IL-6 elevation impaired the development and maturation of dendritic spines.