%A Young,Adam %A Campbell,Elaine %A Lynch,Sarah %A Suckling,John %A Powis,Simon %D 2011 %J Frontiers in Psychiatry %C %F %G English %K autism spectrum condition,Brain,Inflammation,NF-kB,orbitofrontal cortex,pH %Q %R 10.3389/fpsyt.2011.00027 %W %L %M %P %7 %8 2011-May-13 %9 Original Research %+ Dr John Suckling,University of Cambridge,Department of Psychiatry,Herchel Smith Building,Robinson Way,Cambridge,CB2 0SZ,United Kingdom,js369@cam.ac.uk %# %! Aberrant NF-kappaB expression in ASC %* %< %T Aberrant NF-KappaB Expression in Autism Spectrum Condition: A Mechanism for Neuroinflammation %U https://www.frontiersin.org/articles/10.3389/fpsyt.2011.00027 %V 2 %0 JOURNAL ARTICLE %@ 1664-0640 %X Autism spectrum condition (ASC) is recognized as having an inflammatory component. Post-mortem brain samples from patients with ASC display neuroglial activation and inflammatory markers in cerebrospinal fluid, although little is known about the underlying molecular mechanisms. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein found in almost all cell types and mediates regulation of immune response by inducing the expression of inflammatory cytokines and chemokines, establishing a feedback mechanism that can produce chronic or excessive inflammation. This article describes immunodetection and immunofluorescence measurements of NF-κB in human post-mortem samples of orbitofrontal cortex tissue donated to two independent centers: London Brain Bank, Kings College London, UK (ASC: n = 3, controls: n = 4) and Autism Tissue Program, Harvard Brain Bank, USA (ASC: n = 6, controls: n = 5). The hypothesis was that concentrations of NF-κB would be elevated, especially in activated microglia in ASC, and pH would be concomitantly reduced (i.e., acidification). Neurons, astrocytes, and microglia all demonstrated increased extranuclear and nuclear translocated NF-κB p65 expression in brain tissue from ASC donors relative to samples from matched controls. These between-groups differences were increased in astrocytes and microglia relative to neurons, but particularly pronounced for highly mature microglia. Measurement of pH in homogenized samples demonstrated a 0.98-unit difference in means and a strong (F = 98.3; p = 0.00018) linear relationship to the expression of nuclear translocated NF-κB in mature microglia. Acridine orange staining localized pH reductions to lysosomal compartments. In summary, NF-κB is aberrantly expressed in orbitofrontal cortex in patients with ASC, as part of a putative molecular cascade leading to inflammation, especially of resident immune cells in brain regions associated with the behavioral and clinical symptoms of ASC.