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Geroscience. 2019 Aug 31. doi: 10.1007/s11357-019-00089-9. [Epub ahead of print]

Lipopolysaccharide exposure in a rat sepsis model results in hippocampal amyloid-β plaque and phosphorylated tau deposition and corresponding behavioral deficits.

Author information

1
Center for Quantitative Cancer Imaging, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
2
Department of Psychology (Professor Emeritus), University of Utah, Salt Lake City, UT, USA.
3
Department of Radiology and Imaging Sciences, University of Utah, 20 N 1900 E, Room 1A071, Salt Lake City, UT, 84132, USA.
4
Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
5
Oklahoma Nathan Shock Aging Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
6
Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
7
Department of Radiology and Imaging Sciences, University of Utah, 20 N 1900 E, Room 1A071, Salt Lake City, UT, 84132, USA. kathryn.morton@hsc.utah.edu.

Abstract

Sepsis is a severe systemic inflammatory response to infection associated with acute and chronic neurocognitive consequences, including an increased risk of later-life dementia. In a lipopolysaccharide-induced rat sepsis model, we have demonstrated neuroinflammation, cortical amyloid-beta plaque deposition, and increased whole brain levels of phosphorylated tau. Hippocampal abnormalities, particularly those of the dentate gyrus, are seen in Alzheimer's disease and age-related memory loss. The focus of this study was to determine whether Aβ plaques and phosphorylated tau aggregates occur in the hippocampus as a consequence of lipopolysaccharide administration, and whether behavioral abnormalities related to the hippocampus, particularly the dentate gyrus, can be demonstrated. Male Sprague Dawley rats received an intraperitoneal injection of 10 mg/kg of lipopolysaccharide endotoxin. Control animals received a saline injection. Seven days post injection, Aβ plaques and phosphorylated tau in the hippocampus were quantified following immunostaining. Behavioral tests that have previously been shown to result in specific deficits in dentate gyrus-lesioned rats were administered. Lipopolysaccharide treatment results in the deposition of beta amyloid plaques and intracellular phosphorylated tau in the hippocampus, including the dorsal dentate gyrus. Lipopolysaccharide treatment resulted in behavioral deficits attributable to the dorsal dentate gyrus, including episodic-like memory function that primarily involves spatial, contextual, and temporal orientation and integration. Lipopolysaccharide administration results in hippocampal deposition of amyloid-beta plaques and intracellular phosphorylated tau and results in specific behavioral deficits attributable to the dorsal dentate gyrus. These findings, if persistent, could provide a basis for the higher rate of dementia in longitudinal studies of sepsis survivors.

KEYWORDS:

Amyloid beta; Hippocampus; Lipopolysaccharide; Rat; Sepsis; Tauopathy

PMID:
31473912
DOI:
10.1007/s11357-019-00089-9

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