Cognitive deficits found in a pro-inflammatory state are independent of ERK 1/2 signaling in the murine brain hippocampus treated with Shiga toxin 2 from enterohemorrhagic Escherichia Coli

Berdasco, C.; Pinto, A.; Blake, M.; Correa, F.; Longo Carbajosa, N. A.; Geogeghan, P. A.; Cangelosi, A.; Gironacci, M. M.; Goldstein, J.

doi:10.1101/2020.08.24.264929

bioRxiv · 10.1101/2020.08.24.264929

Cognitive deficits found in a pro-inflammatory state are independent of ERK 1/2 signaling in the murine brain hippocampus treated with Shiga toxin 2 from enterohemorrhagic Escherichia Coli

Berdasco, C.·Pinto, A.·Blake, M.·Correa, F.·Longo Carbajosa, N. A.·Geogeghan, P. A.·Cangelosi, A.·Gironacci, M. M.·Goldstein, J.

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Abstract

Shiga toxin 2 (Stx2) from enterohemorrhagic Escherichia coli (EHEC) produces hemorrhagic colitis, hemolytic uremic syndrome (HUS) and acute encephalopathy. The mortality rate in HUS increases significantly when the central nervous system (CNS) is involved. Besides, EHEC also releases lipopolysaccharide (LPS). Many reports have described cognitive dysfunctions in HUS patients, the hippocampus being one of the brain areas targeted by EHEC infection. In this context, a translational murine model of encephalopathy was employed to establish the deleterious effects of Stx2 and the contribution of LPS in the hippocampus. Results demonstrate that systemic administration of a sublethal dose of Stx2 reduced memory index and produced depression like behavior, pro-inflammatory cytokine release and NF-kB activation independent of the ERK 1/2 signaling pathway. On the other hand, LPS activated NF-kB dependent on ERK 1/2 signaling pathway. Cotreatment of Stx2 with LPS aggravated the pathologic state, while dexamethasone treatment succeeded in preventing behavioral alterations. Our present work suggests that the use of drugs such as corticosteroids or NF-kB signaling inhibitors may serve as neuroprotectors from EHEC infection.

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Berdasco, C., Pinto, A., Blake, M., Correa, F., Longo Carbajosa, N. A., Geogeghan, P. A., Cangelosi, A., Gironacci, M. M., Goldstein, J.. 2020-08-24. Cognitive deficits found in a pro-inflammatory state are independent of ERK 1/2 signaling in the murine brain hippocampus treated with Shiga toxin 2 from enterohemorrhagic Escherichia Coli. https://doi.org/10.1101/2020.08.24.264929

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