1. Cytokines expression from altered motor thalamus and behavior deficits following sublethal administration of Shiga toxin 2a involve the induction of the globotriaosylceramide receptor.
- Author
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Arenas-Mosquera D, Pinto A, Cerny N, Berdasco C, Cangelosi A, Geoghegan PA, Malchiodi EL, De Marzi M, and Goldstein J
- Subjects
- Animals, Cytokines metabolism, Escherichia coli metabolism, Lipopolysaccharides toxicity, Mice, Shiga Toxin metabolism, Thalamus metabolism, Trihexosylceramides, Escherichia coli Infections, Shiga Toxin 2 toxicity
- Abstract
Encephalopathy associated with hemolytic uremic syndrome is produced by enterohemorrhagic E. coli (EHEC) infection, which releases the virulence factors Shiga toxin (Stx) and lipopolysaccharide (LPS). Neurological compromise is a poor prognosis and mortality factor of the disease, and the thalamus is one of the brain areas most frequently affected. We have previously demonstrated the effectiveness of anti-inflammatory drugs to ameliorate the deleterious effects of these toxins. However, the thalamic production of cytokines involved in pro-inflammatory processes has not yet been acknowledged. The aim of this work attempts to determine whether systemic sublethal Stx2a or co-administration of Stx2a with LPS are able to rise a proinflammatory profile accompanying alterations of the neurovascular unit in anterior and lateral ventral nuclei of the thalamus (VA-VL) and motor behavior in mice. After 4 days of treatment, Stx2a affected the lectin-bound microvasculature distribution while increasing the expression of GFAP in reactive astrocytes and producing aberrant NeuN distribution in degenerative neurons. In addition, increased swimming latency was observed in a motor behavioral test. All these alterations were heightened when Stx2a was co-administered with LPS. The expression of pro-inflammatory cytokines TNFα, INF-γ and IL-2 was detected in VA-VL. All these effects were concomitant with increased expression of the Stx receptor globotriaosylceramide (Gb3), which hints at receptor involvement in the neuroinflammatory process as a key finding of this study. In conclusion, Stx2a to Gb3 may be determinant in triggering a neuroinflammatory event, which may resemble clinical outcomes and should thus be considered in the development of preventive strategies., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2022
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