Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors.
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.
Department of Neurochemistry, NY State Institute for Basic Research in Developmental Disabilities, New York, NY 10314, USA.
Hongen
H
Wei
Kathryn K
KK
Chadman
Daniel P
DP
McCloskey
Ashfaq M
AM
Sheikh
Mazhar
M
Malik
W Ted
WT
Brown
Xiaohong
X
Li
D000818:Animals; D001007:Anxiety; D001321:Autistic Disorder / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D003071:Cognition; D049229:Dendritic Spines / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D019706:Excitatory Postsynaptic Potentials; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D053444:Inhibitory Postsynaptic Potentials; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics / Q000276:immunology
D015850:Interleukin-6; D049452:Green Fluorescent Proteins