Intracerebroventricular Shiga toxin 2 increases the expression of its receptor globotriaosylceramide and causes dendritic abnormalities

Tironi-Farinati, Carla; Loidl, César Fabián; Boccoli, Javier; Parma, Yanil; Fernández‐Miyakawa, Mariano E.; Goldstein, Jorge

doi:10.1016/j.jneuroim.2010.03.001

Cited by 31 publications

(32 citation statements)

References 59 publications

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“…It is tempting to speculate that the high levels of CD77 are a direct response to Stx exposure in an effort to limit toxic effects. This is in line with an animal study showing that intracerebroventricular administration of Stx2 in rat brains is associated with significantly increased levels of CD77/Gb3 in neurons (23). Further studies to investigate CD77/Gb3 expression on neurons in EHEC patients without neurological symptoms would help to clarify this matter.…”

Section: Discussionsupporting

confidence: 87%

Upregulation of Shiga Toxin Receptor CD77/Gb3 and Interleukin‐1β Expression in the Brain of EHEC Patients with Hemolytic Uremic Syndrome and Neurologic Symptoms

et al. 2014

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In 2011, a large outbreak of Shiga toxin-producing enterohemorrhagic Escherichia coli (EHEC) infections occurred in northern Germany, which mainly affected adults. Out of 3842 patients, 104 experienced a complicated course comprising hemolytic uremic syndrome and neurological complications, including cognitive impairment, aphasia, seizures and coma. T2 hyperintensities on magnet resonance imaging (MRI) bilateral in the thalami and in the dorsal pons were found suggestive of a metabolic toxic effect. Five of the 104 patients died because of toxic heart failure. In the present study, the post-mortem neuropathological findings of the five EHEC patients are described. Histological investigation of 13 brain regions (frontal, temporal, occipital cortex, corpora mammillaria, thalamus, frontal operculum, corona radiata, gyrus angularis, pons, medulla oblongata, cerebellar vermis and cerebellar hemisphere) showed no thrombosis, ischemic changes or fresh infarctions. Further, no changes were found in electron microscopy. In comparison with five age-matched controls, slightly increased activation of microglia and a higher neuronal expression of interleukin-1β and of Shiga toxin receptor CD77/globotriaosylceramide 3 was observed. The findings were confirmed by Western blot analyses. It is suggested that CD77/globotriaosylceramide upregulation may be a consequence to Shiga toxin exposure, whereas increased interleukin-1β expression may point to activation of inflammatory cascades.

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Section: Discussionsupporting

confidence: 87%

Upregulation of Shiga Toxin Receptor CD77/Gb3 and Interleukin‐1β Expression in the Brain of EHEC Patients with Hemolytic Uremic Syndrome and Neurologic Symptoms

et al. 2014

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“…These physiological parameters and renal damages, that were comparable to those previously described (29), were partially prevented with C-9. We have demonstrated that Stx2 affects not only the kidney but also the brain of the rats (20) where an increase of Gb3 expression was observed (30). Rats have probably died as a result of both, kidney and extra kidney susceptibility to Stx2.…”

Section: Discussionmentioning

confidence: 79%

A Glucosylceramide Synthase Inhibitor Protects Rats Against the Cytotoxic Effects of Shiga Toxin 2

et al. 2011

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Postdiarrhea hemolytic uremic syndrome is the most common cause of acute renal failure in children in Argentina. Renal damage has been strongly associated with Shiga toxin (Stx), which binds to the globotriaosylceramide (Gb3) receptor on the plasma membrane of target cells. The purpose of the study was to evaluate the in vivo effects of C-9, a potent inhibitor of glucosylceramide synthase and Gb3 synthesis, on kidney and colon in an experimental model of hemolytic uremic syndrome in rats. Rats were i.p. injected with supernatant from recombinant Escherichia coli expressing Stx2 (sStx2). A group of these rats were orally treated with C-9 during 6 d, from 2 d prior until 4 d after sStx2 injection. The injection of sStx2 caused renal damage as well as a loss of goblet cells in colonic mucosa. Oral treatment with C-9 significantly decreased rat mortality to 50% and reduced the extension of renal and intestinal injuries in the surviving rats. The C-9 also decreased Gb3 and glucosylceramide expression levels in rat kidneys. It is particularly interesting that an improvement was seen when C-9 was administered 2 d before challenge, which makes it potentially useful for prophylaxis. (Pediatr Res 69: 390-394, 2011)

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“…The Gb3 was described to be localized in neurons and endothelial cells of the human CNS and in neurons of normal and Stx2 exposed mice [15]. Intracerebroventricular administration of Stx2 in rat brains increased the expression of Gb3 in neurons from striatum, hippocampus and cortex [16], and induced striatal neuronal death as well as glial alteration with perivascular astrocyte cytoplasmic edema and astrocyte gliofilament hypertrophy [17].…”

Section: Introductionmentioning

confidence: 99%

Intraperitoneal administration of Shiga toxin 2 induced neuronal alterations and reduced the expression levels of aquaporin 1 and aquaporin 4 in rat brain

Lucero

Mirarchi

Goldstein

et al. 2012

Microbial Pathogenesis

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Intracerebroventricular Shiga toxin 2 increases the expression of its receptor globotriaosylceramide and causes dendritic abnormalities

Cited by 31 publications

References 59 publications

Upregulation of Shiga Toxin Receptor CD77/Gb3 and Interleukin‐1β Expression in the Brain of EHEC Patients with Hemolytic Uremic Syndrome and Neurologic Symptoms

Upregulation of Shiga Toxin Receptor CD77/Gb3 and Interleukin‐1β Expression in the Brain of EHEC Patients with Hemolytic Uremic Syndrome and Neurologic Symptoms

A Glucosylceramide Synthase Inhibitor Protects Rats Against the Cytotoxic Effects of Shiga Toxin 2

Intraperitoneal administration of Shiga toxin 2 induced neuronal alterations and reduced the expression levels of aquaporin 1 and aquaporin 4 in rat brain

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