Original Research ARTICLE

Front. Psychiatry, 13 May 2011 | http://dx.doi.org/10.3389/fpsyt.2011.00027

Aberrant NF-kappaB expression in autism spectrum condition: a mechanism for neuroinflammation

Adam M. H. Young1,2, Elaine Campbell1, Sarah Lynch1, John Suckling3* and Simon J. Powis1
  • 1 Bute Medical School, University of St. Andrews, Fife, Scotland, UK
  • 2 Autism Research Unit, Department of Psychiatry, University of Cambridge, Cambridge, UK
  • 3 Department of Psychiatry, University of Cambridge, Cambridge, UK

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.

Keywords: NF-κB, autism spectrum condition, brain, inflammation, orbitofrontal cortex, pH

Citation: Young AMH, Campbell E, Lynch S, Suckling J and Powis SJ (2011) Aberrant NF-kappaB expression in autism spectrum condition: a mechanism for neuroinflammation. Front. Psychiatry 2:27. doi: 10.3389/fpsyt.2011.00027

Received: 10 December 2010; Accepted: 03 May 2011;
Published online: 13 May 2011.

Edited by:

Lin He, Shanghai Jiao Tong University, China

Reviewed by:

Gráinne Mcalonan, University of Hong Kong, Hong Kong
Elizabeth Maria Sajdel-Sulkowska, Harvard Medical School, Brigham and Women’s Hospital, USA

Copyright: © 2011 Young, Campbell, Lynch, Suckling and Powis. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

*Correspondence: John Suckling, Department of Psychiatry, University of Cambridge, Herchel Smith Building, Robinson Way, Cambridge CB2 0SZ, UK. e-mail: js369@cam.ac.uk