Relationship between Liver Pathology and Disease Progression in a Murine Model of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes selective motor neuron cell death and accompanying skeletal muscle atrophy and structural deformities. In both patients with ALS and animal models, there appears to be spinal cord and muscle pathology. This pathology can be modeled in hSOD1G93A mice, which have a point mutation in the gene for superoxide dismutase 1. Similar to patients with ALS, hSOD1G93A mice present hepatic abnormalities and lymphocytic infiltration in the liver. However, the relationship between liver function and disease progression is not well understood.The goal of this study was to investigate the molecular mechanisms relating liver pathology to disease progression in hSOD1G93A mice.Liver tissues were harvested from control (nontransgenic) mice, presymptomatic hSOD1G93A mice, and symptomatic hSOD1G93A mice.In the liver, the expression of proteins related to inflammation and oxidative stress increased with disease progression in hSOD1G93A mice. Furthermore, histone deacetylase 4, DNA-damage-inducible 45α, and platelet-derived growth factor β, which are associated with liver fibrosis, were upregulated in the livers of presymptomatic hSOD1G93A mice.Taken together, these findings suggest that liver dysfunction in hSOD1G93A transgenic mice is mediated by increased inflammation and oxidative stress as well as the upregulation of fibrosis-related proteins.