title: Shiga Toxin Mediated Neurologic Changes in Murine Model of Disease.
abstract: Seizures and neurologic involvement have been reported in patients infected with Shiga toxin (Stx) producingE. coli, and hemolytic uremic syndrome (HUS) with neurologic involvement is associated with more severe outcome. We investigated the extent of renal and neurologic damage in mice following injection of the highly potent form of Stx, Stx2a, and less potent Stx1. As observed in previous studies, Stx2a brought about moderate to acute tubular necrosis of proximal and distal tubules in the kidneys. Brain sections stained with hematoxylin and eosin (H&E) appeared normal, although some red blood cell congestion was observed. Microglial cell responses to neural injury include up-regulation of surface-marker expression (e.g., Iba1) and stereotypical morphological changes. Mice injected with Stx2a showed increased Iba1 staining, mild morphological changes associated with microglial activation (thickening of processes), and increased microglial staining per unit area. Microglial changes were observed in the cortex, hippocampus, and amygdala regions, but not the nucleus. Magnetic resonance imaging (MRI) of Stx2a-treated mice revealed no hyper-intensities in the brain, although magnetic resonance spectroscopy (MRS) revealed significantly decreased levels of phosphocreatine in the thalamus. Less dramatic changes were observed following Stx1 challenge. Neither immortalized microvascular endothelial cells from the cerebral cortex of mice (bEnd.3) nor primary human brain microvascular endothelial cells were found to be susceptible to Stx1 or Stx2a. The lack of susceptibility to Stx for both cell types correlated with an absence of receptor expression. These studies indicate Stx causes subtle, but identifiable changes in the mouse brain.
authors.affiliation: Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati Cincinnati, OH, USA.
authors.forename: Suman
authors.initials: S
authors.lastname: Pradhan
authors.affiliation: KAO USA Inc. Cincinnati, OH, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Pellino
authors.affiliation: Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati Cincinnati, OH, USA.
authors.forename: Kayleigh
authors.initials: K
authors.lastname: MacMaster
authors.affiliation: Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati Cincinnati, OH, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Coyle
authors.affiliation: Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati Cincinnati, OH, USA.
authors.forename: Alison A
authors.initials: AA
authors.lastname: Weiss
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins; D018929:Cell Culture Techniques; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000378:metabolism / Q000472:pathogenicity; D006463:Hemolytic-Uremic Syndrome / Q000382:microbiology / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D008840:Microfilament Proteins; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009420:Nervous System / Q000187:drug effects* / Q000473:pathology*; D010725:Phosphocreatine / Q000032:analysis; D011817:Rabbits; D012097:Repressor Proteins; D022621:Shiga Toxin / Q000008:administration & dosage / Q000633:toxicity*; D022641:Shiga Toxin 2 / Q000008:administration & dosage / Q000633:toxicity; D013057:Spectrum Analysis / Q000379:methods; D013788:Thalamus / Q000737:chemistry; D018675:Toxicity Tests / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015430:Weight Gain / Q000187:drug effects; D015431:Weight Loss / Q000187:drug effects
chemical_list: C491049:Aif1 protein, mouse; C000595575:BEND3 protein, mouse; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D012097:Repressor Proteins; D022641:Shiga Toxin 2; D014409:Tumor Necrosis Factor-alpha; D010725:Phosphocreatine; D022621:Shiga Toxin
keywords: H&E staining; Iba1 antibody; bacterial toxin; microglia activation; mouse brain