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  • Poster presentation
  • Open Access

Peripheral inflammation increases PKR activation, Tau phosphorylation and amyloid β production in wild-type mice

  • 1, 2,
  • 1,
  • 1,
  • 1,
  • 1, 3,
  • 1, 2 and
  • 1, 2
Molecular Neurodegeneration20138 (Suppl 1) :P32

https://doi.org/10.1186/1750-1326-8-S1-P32

  • Published:

Keywords

  • Learn Objective
  • Dependent Protein Kinase
  • Peripheral Inflammation
  • Sickness Behaviour
  • Serum Cytokine Level

Background

Systemic inflammation is correlated with dementia progression. Pro-inflammatory molecules can communicate from the periphery to the central nervous system to induce neuroinflammation and neurodegeneration. Our protein of interest is the pro-apoptotic kinase PKR (the double strand-RNA dependent protein kinase). Increased activated PKR levels were found in AD patients brain and cerebrospinal fluid. PKR activation can be triggered by inflammatory stresses and induces neurotoxicity in vitro. Is in vivo PKR-mediated inflammation involved in AD neurodegenerative process?

Learning objective

To investigate whether PKR-mediated neuroinflammation could play a role in AD neurodegenerative process.

Methods

C57BL/6 wild type mice were injected intraperitoneally with LPS (1mk/kg) versus saline once a day for 3 days to induce PKR activation and neuroinflammation (LPS is the bacilli gram negative endotoxin lipopolysaccharide).

Brains were collected and dissected; immunohistochemistry and western blotting were performed for neuroinflammation, PKR activation and AD pathological hallmarks (as Tau hyperphosphorylation).

Results

Mice showed endotoxin-induced sickness behaviour includingbody weight loss and elevated serum cytokine levels.

Microglial activation, neuronal apoptosis, increase of PKR, GSK3β and Tau phosphorylation and amyloid β production were found in hippocampus and cortex of LPS-treated mice.

Conclusions

PKR could be involved in the signalling of neurofibrillary tangles formation after a systemic inflammatory challenge.

Authors’ Affiliations

(1)
Inserm UMR-S839, Paris, France
(2)
Hopital Lariboisière APHP, Paris, France
(3)
University of Southampton, Southampton, UK

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