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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2016

Open Access 01-12-2016 | Research

Assessment of neuroinflammation in a mouse model of obesity and β-amyloidosis using PET

Authors: Anna M. Barron, Masaki Tokunaga, Ming-Rong Zhang, Bin Ji, Tetsuya Suhara, Makoto Higuchi

Published in: Journal of Neuroinflammation | Issue 1/2016

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Abstract

Background

Obesity has been identified as a risk factor for cognitive decline and Alzheimer’s disease (AD). The aim of this study was to investigate the effect of obesity on neuroinflammation and cerebral glucose metabolism using PET in a mouse model of β-amyloidosis and determine the relationship between these PET imaging biomarkers, pathogenic changes, and functional outcomes.

Methods

Three-month-old C57BL/J6 mice were fed either a standard (control group) or high-fat diet (obese group) for 3 months and intracerebroventricularly infused with vehicle or human beta amyloid 1-42 (Aβ42). We assessed obesity-induced abnormalities in peripheral metabolic indices including adiposity, fasting glucose, and glucose tolerance. Brain glucose metabolism was assessed by 18F-FDG PET, and glial activation was assessed using the translocator protein (TSPO) ligand 11C-PBR-28. TSPO expression was confirmed by immunohistochemistry of brain sections obtained from scanned mice. The association between inflammatory state and 11C-PBR-28 PET signals was characterized by examination of the cytokine expression profile in both the serum and hippocampus by antibody array. Learning and memory performance was assessed in the object recognition task, and anxiety-related behavior was assessed in the elevated plus maze.

Results

Obesity combined with Aβ infusion promoted neuroinflammation and cerebral hypermetabolism, and these signals were significant predictors of learning and memory performance in the object recognition task. In vivo TSPO signals were associated with inflammatory markers including CXCL1, CXCL2, CXCL12, CCL3, CCL5, TIMP-1, G-CSF, sICAM-1, and IL-1ra.

Conclusions

In vivo cerebral metabolism and TSPO signals indicate that obesity can accelerate amyloid-induced inflammation and associated cognitive decline.
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Metadata
Title
Assessment of neuroinflammation in a mouse model of obesity and β-amyloidosis using PET
Authors
Anna M. Barron
Masaki Tokunaga
Ming-Rong Zhang
Bin Ji
Tetsuya Suhara
Makoto Higuchi
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2016
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-016-0700-x

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