Cytokine upregulation in a murine model of familial amyotrophic lateral sclerosis

Although pronounced changes in astrocytes and microglia accompany the neuro nal degeneration observed in a murine model of familial amyotrophic lateral sclerosis, the significance of non-neuronal cell contribution to the disea se process remains unclear. Activated astrocytes and microglia are capable of secreting numerous, cytokines, some of which may have potentially harmfu l effects on neuron survival. For this reason we wished to determine the ex pression pattern of various cytokines in the spinal cords of transgenic mic e expressing a Cu-Zn superoxide dismutase mutation (Tgn G93A SOD1) by using semi-quantitative RT-PCB. Three different patterns of cytokine expression were observed in G93A SOD L transgenic mice. For most cytokines, we were un able to detect mRNA expression in Tgn G93A SOD1 mouse spinal cords at any a ge, yet message was readily detected in spleen or activated splenocytes. A second pattern, typified by TNF-a, was characterized by mRNA expression pri or to the onset of motor deficits and increasing until the terminal stages of the disease. For other cytokines, including TGF-beta1 and M-CSF, mRNA ex pression was detected in young presymptomatic Tgn G93A SOD1 mice (as well a s wild-type and transgenic mice expressing wild-type SOD l (Tgn SOD I)), wi th upregulation later occurring only. in G93A SOD1 transgenic mice. These r esults indicate a temporal correlation between the expression of certain cy tokines and the onset of motor dysfunction in Tgn G93A SOD1 mice and sugges t a potential role for these molecules in the disease. (C) 2001 Elsevier Sc ience B V All rights reserved.