Inflammatory and non-inflammatory monocytes as novel prognostic biomarkers of survival in SOD1G93A mouse model of Amyotrophic Lateral Sclerosis.

Abstract

Amyotrophic Lateral Sclerosis (ALS) has lately become a suitable scenario to study the interplay between the hematopoietic system and disease progression. Recent studies in C9orf72 null mice have demonstrated that C9orf72 is necessary for the normal function of myeloid cells. In this study, we aimed to analyze in depth the connection between the hematopoietic system and secondary lymphoid (spleen) and non-lymphoid (liver and skeletal muscle) organs and tissues along the disease progression in the transgenic SOD1G93A mice. Our findings suggested that the inflammatory response due to the neurodegeneration in this animal model affected all three organs and tissues, especially the liver and the skeletal muscle. However, the liver was able to compensate this inflammatory response by means of the action of non-inflammatory monocytes, while in the skeletal muscle inflammatory monocytes prompted a further inflammation process until the terminal state of the animals. Interestingly, in blood, a positive correlation was found between non-inflammatory monocytes and survival of the transgenic SOD1G93A mice, while the contrary (a negative correlation) was found in the case of inflammatory monocytes, supporting their potential role as biomarkers of disease progression and survival in this animal model. These findings could prompt future translational studies in ALS patients, promoting the identification of new reliable biomarkers of disease progression.