Complex Inflammation mRNA-Related Response in ALS Is Region Dependent

[摘要] Inflammatory changes are analyzed in the anterior spinal cord and frontal cortex area 8 in typical spinal-predominant ALS cases. Increased numbers of astrocytes and activated microglia are found in the anterior horn of the spinal cord and pyramidal tracts. Significant increased expression ofTLR7,CTSS, andCTSCmRNA and a trend to increased expression ofIL10RA,TGFB1, andTGFB2are found in the anterior lumbar spinal cord in ALS cases compared to control cases, whereasC1QTNF7andTNFRSF1AmRNA expression levels are significantly decreased.IL6is significantly upregulated andIL1Bshows a nonsignificant increased expression in frontal cortex area 8 in ALS cases. IL-6 immunoreactivity is found in scattered monocyte-derived macrophages/microglia and TNF-αin a few cells of unknown origin in ALS cases. Increased expression and abnormal distribution of IL-1βoccurred in motor neurons of the lumbar spinal cord in ALS. Strong IL-10 immunoreactivity colocalizes with TDP-43-positive inclusions in motor neurons in ALS cases. The present observations show a complex participation of cytokines and mediators of the inflammatory response in ALS consistent with increased proinflammatory cytokines and sequestration of anti-inflammatory IL-10 in affected neurons.

[学科分类] 精神健康和精神病学