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dc.contributor.authorYoung, Adam
dc.contributor.authorCampbell, Elaine Catherine
dc.contributor.authorLynch, Sarah Janice
dc.contributor.authorSuckling, John
dc.contributor.authorPowis, Simon John
dc.identifier.citationYoung , A , Campbell , E C , Lynch , S J , Suckling , J & Powis , S J 2011 , ' Aberrant NF-kappaB expression in autism spectrum condition : a mechanism for neuroinflammation ' , Frontiers in Psychiatry , vol. 2 , 27 .
dc.identifier.otherPURE: 10073156
dc.identifier.otherPURE UUID: 5820e53f-5c03-4eb4-844f-b0ff701a5bf5
dc.identifier.otherScopus: 84862170482
dc.identifier.otherORCID: /0000-0003-4218-2984/work/60195293
dc.description.abstractAutism 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.
dc.relation.ispartofFrontiers in Psychiatryen
dc.rights© 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.en
dc.subjectAutism spectrum conditionen
dc.subjectOrbitofrontal cortexen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.titleAberrant NF-kappaB expression in autism spectrum condition : a mechanism for neuroinflammationen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.description.statusPeer revieweden

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