Artículo
Cytokines expression from altered motor thalamus and behavior deficits following sublethal administration of Shiga toxin 2a involve the induction of the globotriaosylceramide receptor
Arenas Mosquera, David
; Vasconcelos Esteves Pinto, Alipio
; Cerny, Natacha
; Berdasco, Clara Valentina
; Cangelosi, Adriana; Geoghegan, Patricia Andrea; Malchiodi, Emilio Luis
; de Marzi, Mauricio Cesar
; Goldstein Raij, Jorge
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Fecha de publicación:
09/2022
Editorial:
Pergamon-Elsevier Science Ltd
Revista:
Toxicon
ISSN:
0041-0101
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
CYTOKINES
,
GFAP
,
GLOBOTRIAOSYLCERAMIDE
,
LIPOPOLYSACCHARIDE
,
NEUN
,
SHIGA TOXIN
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Identificadores
Colecciones
Articulos(IDEHU)
Articulos de INST.DE EST.DE LA INMUNIDAD HUMORAL PROF.R.A.MARGNI
Articulos de INST.DE EST.DE LA INMUNIDAD HUMORAL PROF.R.A.MARGNI
Articulos(IFIBIO HOUSSAY)
Articulos de INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Articulos de INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Articulos(IMPAM)
Articulos de INSTITUTO DE INVESTIGACIONES EN MICROBIOLOGIA Y PARASITOLOGIA MEDICA
Articulos de INSTITUTO DE INVESTIGACIONES EN MICROBIOLOGIA Y PARASITOLOGIA MEDICA
Articulos(INEDES)
Articulos de INSTITUTO DE ECOLOGIA Y DESARROLLO SUSTENTABLE
Articulos de INSTITUTO DE ECOLOGIA Y DESARROLLO SUSTENTABLE
Citación
Arenas Mosquera, David; Vasconcelos Esteves Pinto, Alipio; Cerny, Natacha; Berdasco, Clara Valentina; Cangelosi, Adriana; et al.; Cytokines expression from altered motor thalamus and behavior deficits following sublethal administration of Shiga toxin 2a involve the induction of the globotriaosylceramide receptor; Pergamon-Elsevier Science Ltd; Toxicon; 216; 9-2022; 115-124
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