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bioRxiv · 10.1101/2022.04.19.488860

Activation of IP10/CXCR3 signaling with highly coincidental with PrPSc deposit in the brains of scrapie infected mice

jia, C.·Chen, c.·chao, H.·wei, Y.·lin, W.·dong, C. d.·zhang, W. y.·qi, S.·ping, D. x.
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Abstract

Activation of chemokine IP10, also named as CXCL10, and its receptor CXCR3 in CNS is described in some neurodegenerative diseases. Our previous study has also demonstrated an increased brain IP10 levels in several scrapie infected rodent models. However, the detailed alteration of IP10/CXCR3 signaling in CNS during prion infection remains unsettled. Here, we found the increased IP10 signals in the brains of scrapie infected mice mainly localized in the neurons and the activated microglia using various methodologies. The levels of CXCR3 were markedly increased in brains of the scrapie infected mice and in the prion infected cell line SMB-S15. The increased CXCR3 mainly distributed in neurons. Obviously morphological colocalizations of PrP/PrPSc with IP10 and CXCR3 in the brains of scrapie infected mice were observed in the assays of immunohistochemistry (IHC) and immunofluorescence. Additionally, IHC analysis with whole brain sections demonstrated that the increased IP10 and CXCR3 accumulated in the brain regions with more PrPSc deposits. Co-immunoprecipitation and biomolecular interaction assays identified the evidence for the molecular interactions of PrP with IP10 and CXCR3. Compared to the normal partner cell line SMB-PS, the more portion of IP10 accumulated insides of prion infected SMB-S15 cells. Removal of prion replication in SMB-S15 cells by resveratrol converted the pattern of the accumulation and secretion of cellular IP10. Our data here demonstrate an activation of IP10/CXCR3 signaling in the brain tissues of prion infection, highly coincidental with PrPSc deposit. Modulation of brain IP10/CXCR3 signaling is potential therapeutic target for reducing the progression of prion diseases.

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jia, C., Chen, c., chao, H., wei, Y., lin, W., dong, C. d., zhang, W. y., qi, S., ping, D. x.. 2022-04-20. Activation of IP10/CXCR3 signaling with highly coincidental with PrPSc deposit in the brains of scrapie infected mice. https://doi.org/10.1101/2022.04.19.488860

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