PARTICIPATION OF THE MICROGLIA IN HIPPOCAMPAL DYSFUNCTION BY SHIGA TOXIN 2 (STX2) FROM ENTEROHEMORRHAGIC Escherichia coli (EHEC) PRODUCING HEMOLYTIC UREMIC SYNDROME

ROSATO-SIRI VICTORIA; BERDASCO CLARA; GOLDSTEIN JORGE

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Stx2 causes bloody colitis, HUS and neurological dysfunctions.Hippocampal cognitive deterioration is observed. EHEC secretesStx2 and releases LPS. The aim was to determine whether sub-lethalStx2 (S), LPS (L) or Stx2 co-administered with LPS (S+L) alteredthe hippocampal neurovascular unit by microglial activation.Male NIH mice (n=4) were injected iv. with: saline (control, C); 800ηgof L; 1ηg of S or 1ηg of S with 800ηg of L (S+L). Fixed brains weresubjected to immunofluorescence with lectins to determine the microvasculatureprofile, anti-GFAP, anti-NeuN and anti-Iba1 to identifyreactive astrocytes, neuronal damage and the microglial staterespectively from 2 to 20 days post injection. Primary microglial cultureswere incubated with either DMEM (C), 1 and 100 ηg/ml of S,or 1 and 100 ηg/ml of S with 800 mg/ml of L (S+L), following heatshock incubation to test microglial activation. Anti-Iba1 and anti-Stx2immunofluorescences were used to identify microglia cells and intracellularStx2 respectively. The deepest hippocampal deteriorationwas observed after 2 days of S+L treatment. S+L and S treatmentsresulted to decrease the area occupied by microvasculature (7.35±0.25 C; 5.25 ±0.38 L; 2.75 ±0.15 S; 1.4 ±0.21 S+L), increased theexpression levels of GFAP (0.19 ±0.02 C; 0.36 ±0.04 L; 0.52 ±0.02S; 0.60 ±0.02 S+L) and decreased the thickness of pyramidal layer(59 ±1.3 C; 48 ±1.44 L; 42 ±1.15 S; 36 ±1.5 S+L) p