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Aberrant NF-kappaB expression in autism spectrum condition : a mechanism for neuroinflammation
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dc.contributor.author | Young, Adam | |
dc.contributor.author | Campbell, Elaine Catherine | |
dc.contributor.author | Lynch, Sarah Janice | |
dc.contributor.author | Suckling, John | |
dc.contributor.author | Powis, Simon John | |
dc.date.accessioned | 2013-01-10T10:31:01Z | |
dc.date.available | 2013-01-10T10:31:01Z | |
dc.date.issued | 2011-05-13 | |
dc.identifier | 10073156 | |
dc.identifier | 5820e53f-5c03-4eb4-844f-b0ff701a5bf5 | |
dc.identifier | 84862170482 | |
dc.identifier.citation | Young , 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 . https://doi.org/10.3389/fpsyt.2011.00027 | en |
dc.identifier.issn | 1664-0640 | |
dc.identifier.other | ORCID: /0000-0003-4218-2984/work/60195293 | |
dc.identifier.uri | https://hdl.handle.net/10023/3324 | |
dc.description.abstract | 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. | |
dc.format.extent | 8 | |
dc.format.extent | 651854 | |
dc.language.iso | eng | |
dc.relation.ispartof | Frontiers in Psychiatry | en |
dc.subject | Autism spectrum condition | en |
dc.subject | Brain | en |
dc.subject | Inflammation | en |
dc.subject | Orbitofrontal cortex | en |
dc.subject | RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry | en |
dc.subject.lcc | RC0321 | en |
dc.title | Aberrant NF-kappaB expression in autism spectrum condition : a mechanism for neuroinflammation | en |
dc.type | Journal article | en |
dc.contributor.institution | University of St Andrews. School of Medicine | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.identifier.doi | 10.3389/fpsyt.2011.00027 | |
dc.description.status | Peer reviewed | en |
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