| Summary: | Autism Spectrum Condition (ASC) is recognised as having an inflammatory component. Post mortem brain samples from patients with ASC display neuroglial activation and inflammatory markers in cerebro-spinal fluid, although little is known about the underlying molecular mechanisms. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) 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 and of NF-kB in human post-mortem samples of orbitofrontal cortex tissue donated to two independent centres: 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-kB would be elevated, especially in activated microglia in ASC, and pH would be concomitantly reduced (i.e. acidification). Neurons, astrocytes and mircroglia all demonstrated increased extranuclear and nuclear translocated NF-kB p65 expression in samples of 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 homogenised 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-kB in mature microglia. Acridine orange staining localised 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 that is potentially responsible for the associated behavioural and clinical symptoms.
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