AMYOTROPHIC LATERAL SCLEROSIS AUTO-ANTIBODIES AND ABSENCE OF P/Q-TYPE CALCIUM CHANNELS

GONZALEZ LAURA E; KOTLER MONICA L; SANCHEZ VIVIANA N; REISIN RICARDO C; UCHITEL OSVALDO D

Huerta Grande

Congreso; IRCN First Joint Meeting of the Argentine Society for Neurosciences (SAN) and the Argentine Workshop in Neurosciences (TAN); 2009

Molecular And Cellular NeurobiologyPoster Number (126) Session IIAMYOTROPHIC LATERAL SCLEROSIS AUTO-ANTIBODIES ANDABSENCE OF P/Q-TYPE CALCIUM CHANNELSGonzalez Laura E 1,2, Kotler Monica L 2, Sanchez Viviana N 3,Reisin Ricardo C 4, Uchitel Osvaldo D 11Departamento de Fisiología, Biología Molecular y Celular, Facultad de CienciasExactas y Naturales, UBA, IFIBYNE-CONICET, 2Departamento de QuímicaBiológica, Facultad de Ciencias Exactas y Naturales, UBA, 3Instituto de BiologíaCelular y Neurociencia, Facultad de Medicina, UBA, 4Servicio de Neurofisiología,Hospital Británico.laurag@qb.fcen.uba.arBackground: Amyotrophic Lateral Sclerosis (ALS) is an invariablyfatal neurodegenerative disease characterized by a gradual loss of superiorand inferior motoneurons. Approximately 90 of ALS cases belongs to asporadic form of the disease, whose etiology is still unknown. Objectives:Previous results from our laboratory (J. Neurosci. 26(10):2661, 2006) favoran autoimmunity hypothesis as a potential cause for sporadic ALS. Inorder to gain knowledge about the possible antigens that interact withImmunoglobulins G from sporadic ALS patients (ALS-IgG), we studied theirimmunoreactivity against NMJ of normal mice and those lacking P/Q- andN-type calcium channels. Methods: We purified Immunoglobulins G (IgGs)from sera of ALS patients by affinity chromatography and characterizedthem by immunofluorescence with a confocal microscope. Results: Inapproximately 50 of cases (5 out of 9), ALS-IgGs presented a strongimmunoreactivity against neuromuscular junctions of mouse diaphragm,colocalizing with Acetylcholine Receptor, a post-synaptic membranemarker of that structure. The representative fluorescence intensity (rfi) forALS-IgGs was 3.97+/-0.76 whereas for control patients it was 1.76+/-0.54(p0.01, N=3). Additionally 4 out of 5 of these sera showed a significantdecrease in their interaction with NMJ of mice lacking P/Q-type calciumchannels (rfi: 2.72+/-0.29, p0.001, N=2), reaching levels comparable withthe isotype control (rfi: 2.31+/-0.38). This difference in reactivity wascompletely absent when N-type calcium channel wild-type and knockoutmice were used (rfi: 16.47+/-1.18 for WT and 17.35+/-1.27 for KO,N=2). Conclusions: The results found in this work add evidence in favor ofULTIMO_2.indd 199 26/08/2009 2:55:29