ANTI-INFLAMMATORY AGENTS RESCUE NEURONAL DAMAGE AND MOTOR DEFICITS FROM SHIGA TOXIN 2 AND LIPOPOLYSACCHARIDE IN THE BRAIN STRIATUM OF RODENTS.

PINTO ALIPIO; DAVID ARENAS; CANGELOSI ADRIANA; GEOGHEGAN PATRICIA; BRENER GABRIELA; GOLDSTEIN JORGE

Boston, Massachusetts

Simposio; 9th Triennial International Symposium on Shiga Toxin (Verocytotoxin)-producing Escherichia coli (VTEC) meeting; 2015

ANTI-INFLAMMATORY AGENTS RESCUE NEURONAL DAMAGE AND MOTOR DEFICITS FROM SHIGA TOXIN 2 AND LIPOPOLYSACCHARIDE IN THE BRAIN STRIATUM OF RODENTS. Alipio Pinto1*, David Arenas1, Adriana Cangelosi2, Patricia Geoghegan2, Gabriela Brener1, Jorge Goldstein1.1 Instituto de Fisiología y Biofísica "Houssay" IFIBIO, CONICET/UBA.2 Centro Nacional de Control de Calidad de Biológicos (CNCCB), ANLIS ?Dr. Carlos G. Malbrán?.*Presenting author: A. Pinto (pintoalipio@gmail.com)Introduction: The striatum is involved in central motor pathways and is frequently affected in patients infected with EHEC. In addition to Stx2, LPS is secreted by the bacteria and may also contribute to the observed striatal dysfunction. The aim of this study was to determine: i) whether LPS exacerbates the deleterious effect of Stx2, ii) whether Stx2 alters the motor performance, and iii) the existence of a pro-inflammatory component. Methods: NIH male mice were injected intravenously with Stx2+LPS or Stx2 or LPS or vehicle (control). In addition the same described groups were treated with Dexamethasone. Mice were perfused with fixative solution. Their brains were subjected to immunofluorescence with an anti-NeuN (Neuronal nuclei marker), anti-MAP2 to identify fibers and anti-Gb3 (Stx2 receptor). Open field test were assayed to study motor performance. Also SD male rats were injected intracerebroventricular with Stx2 (20 pg/gr) and Stx2+Etanercept (3.10 ηM, soluble TNF-α receptor) to immunolocalize Stx2 in striatal neurons by immuno-gold electron microscopy. Results and Discussion: Stx2+LPS maximally increased the neuronal damage (34+4%), decreased the expression levels of MAP2 (31+0.57 in arbitrary units [AU]) and increased the expression levels of Gb3 (85+7.57 AU). Mice treated with Stx2+LPS showed an altered motor performance (64+11% less) in comparison to controls. Dexamethasone significantly reverted the changes observed on NeuN, MAP2 and Gb3 expresion and in motor performace. Etanercept reduced the damaged produced by Stx2, and reduced the immuno-gold particles that corresponded to Stx2 into striatal neurons (P