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Peripheral inflammation increases PKR activation, Tau phosphorylation and amyloid β production in wild-type mice
© Mouton-Liger et al; licensee BioMed Central Ltd. 2013
Published: 13 September 2013
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?
To investigate whether PKR-mediated neuroinflammation could play a role in AD neurodegenerative process.
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).
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.
PKR could be involved in the signalling of neurofibrillary tangles formation after a systemic inflammatory challenge.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.