IgGs from sporadic Amyotrophic Lateral Sclerosis patients induce neurodegeneration and microglia activation in mouse-isolated spinal cord model

BRUNO DE AMBROSI; GIULIANA C DI MAURO; GRACIELA L MAZZONE; OSVALDO D UCHITEL; BRUNO DE AMBROSI; GIULIANA C DI MAURO; GRACIELA L MAZZONE; OSVALDO D UCHITEL

Córdoba

Congreso; Sociedad Argentina de Investigación en Neurociencias; 2018

Amyotrophic Lateral Sclerosis (ALS) has as a target upper and lower motoneurons. Our previous studies have demonstrated the pathological role of autoimmune mechanisms mediated by antibodies in sporadic ALS patients. In the present study, we tested the effect of IgG from a group of sporadic ALS patients on the mouse-isolated spinal cord preparation, which was incubated with different ALS and control sera for 6 h. The purpose of the present study was to characterize (by immunohistochemistry) the localization of IgG in neurons and their role in microglia activation. Our results demonstrated significant IgG immunoreactivity in interneurons from dorsal and ventral spinal cord areas, and motoneurons. Furthermore, after applying ALS sera the number of ventral neurons was significantly decreased. On the contrary, while no changes in the number of microglia were observed, analysis of morphological parameters of microglial cells showed branche length to be significantly decreased following ALS serum incubation. Indeed, a significantly increase in CD68 staining, a marker for activated microglia, was observed that was consistent with post-transcriptional microglia activation while no effect was observed in the CD68 mRNA analysed by RT-PCR. These findings indicate the presence of a neuroinflammatory process in the pathological event induced by sporadic ALS sera and support the hypothesis of autoimmunity in the development of this neurodegenerative disease.