Hippocampal damage caused by Shiga toxin type 2 (Stx2) from enterohemorrhagic Escherichia coli: a translational murine model

BERDASCO CLARA; GEOGHEGAN PATRICIA; PINTO ALIPIO; CANGELOSI ADRIANA; ARENAS DAVID; GOLDSTEIN JORGE

Ciudad Autonoma de Buenos Aires

Congreso; III International Congress in Translational Medicine; 2016

Facultad de Farmacia y Bioquimica y Facultad de Medicina UBA

Stx2 may damage the CNS independently or concomitantly with Hemolytic Uremic Syndrome (HUS). A proinflamatory agent may play a critical role on neuronal impairment in the pathology. Cognitive dysfunction of patients occurs following intoxication with Stx2. The aim of this study was to determine the changes in the hippocampus after intravenous administration of a sub-lethal dose of Stx2 and the inflammatory contribution for the cerebral damage by morphometric and behavior studies. Male NIH mice (30g) were injected intravenously (i.v) with vehicle (control group), 0.5ηg of Stx2 per mouse (sub-lethal dose). Mice were intracardially perfused with a fixative solution. Their brains were subjected to immunofluorescence with lectins (Licopersicum sculentum) to identify the microvasculature (two variables were observed: the number of lectin immunopositive particles and the area occupied by these particles) and anti-GFAP to identify astrocytes (two variables were observed: the number of astrocytes and the expression level of GFAP). Also, other mice injected intravenously with the same described groups, were treated with 2 intraperitoneal injections of saline solution or with the anti-inflammatory Dexamethasone (7,5mg/kg) twice a day for 4 days (day of the i.v. injection as day 0). On the fourth day of treatment, the forced swimming behavior test (FST) was assayed to study the hippocampal function (the variable observed was the immobility time). The t-test was done to analyze the results. Sub-lethal Stx2 significantly increased the number of lectin immunopositive particles (18±1.42, vehicle vs 32±2.24, Stx2) (p