Serum IgG from ALS patients induced neuronal uptake and microglia activation in spinal cord cultures

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

Ciudad Autónoma de Buenos Aires

Congreso; 2nd Federation of Latin-American and Caribbean Societies for Neuroscience (FALAN) Congress; 2016

We have demonstrated that motor nerve terminals are a target for autoimmune response induced by IgG from amyotrophic lateral sclerosis (ALS) patients causing neuromuscular dysfunction in vivo (Pagani R et al, J Neurosci. 2006, 10:2661-72). Spinal cord cultures are an advantageous test system for exploring disease mechanisms (Mazzone et al, Neuroscience 2010, 168:451?62). Our present goal was to study the effect of IgG from ALS patients on neurons and microglia at mice neonatal spinal cord. The spinal cord reactivity to IgG-ALS serum patients was analyzed by dot-blot and multi-rule Shewhart chart methodology, for control (N=5) and ALS serum patients (N=18). Spinal cord isolated cultures were incubated with IgG from serum patients and histological analysis for neurons (NeuN) and microglia (Iba-1) was performed. Our earlier experiments had proved that IgG derivative from two patients are accumulated in NeuN positive cells. A significant reduction in the number of ventral interneurons was observed (sham: 97.75±1.88 vs patient: 54.28±1.65, p≤0.001, N=4-7). No changes in microglia number were found, but we observed a significant reduction in branches length (sham: 7.12±0.32, patients: 5.39±0.177 and 4.74±0.75, p≤0.05, N=4-8). Our data suggests an ongoing pathological process as was previously demonstrated in vivo. Here we have shown that spinal cord isolated cultures could be a useful model to characterize the molecular mechanism for progressive neurodegenerative diseases in vitro.