LPS-induced systemic inflammation reveals an immunomodulatory role for the prion protein at the blood-brain interface

Journal of Neuroinflammation
Øyvind SalvesenCecilie Ersdal

Abstract

The cellular prion protein (PrPC) is an evolutionary conserved protein abundantly expressed not only in the central nervous system but also peripherally including the immune system. A line of Norwegian dairy goats naturally devoid of PrPC (PRNP Ter/Ter) provides a novel model for studying PrPC physiology. In order to explore putative roles for PrPC in acute inflammatory responses, we performed a lipopolysaccharide (LPS, Escherichia coli O26:B6) challenge of 16 goats (8 PRNP +/+ and 8 PRNP Ter/Ter) and included 10 saline-treated controls (5 of each PRNP genotype). Clinical examinations were performed continuously, and blood samples were collected throughout the trial. Genome-wide transcription profiles of the choroid plexus, which is at the blood-brain interface, and the hippocampus were analyzed by RNA sequencing, and the same tissues were histologically evaluated. All LPS-treated goats displayed clinical signs of sickness behavior, which were of significantly (p < 0.01) longer duration in animals without PrPC. In the choroid plexus, a substantial alteration of the transcriptome and activation of Iba1-positive cells were observed. This response included genotype-dependent differential expression of several genes associated with...Continue Reading

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Citations

Jun 27, 2017·PloS One·Giulia MalachinMaren K Bakkebø
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Methods Mentioned

BETA
transgenic
light microscopy
chips
PCR
RNAseq

Software Mentioned

TopHat2
Excel
DEGSeq2
GraphPad Prism
GraphPad
PANTHER
ADVIA 120

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