title: Assessment of neuroinflammation in a mouse model of obesity and β-amyloidosis using PET.
abstract: 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.
  
  
  
  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 (18)F-FDG PET, and glial activation was assessed using the translocator protein (TSPO) ligand (11)C-PBR-28. TSPO expression was confirmed by immunohistochemistry of brain sections obtained from scanned mice. The association between inflammatory state and (11)C-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.
  
  
  
  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.
  
  
  
  In vivo cerebral metabolism and TSPO signals indicate that obesity can accelerate amyloid-induced inflammation and associated cognitive decline.
authors: Department of Functional Brain Imaging Research, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba-shi, Chiba, 263-8555, Japan.|Neurobiology of Aging and Disease Laboratory, Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Drive, Singapore, 636921, Singapore.
authors: Anna M
authors: AM
authors: Barron
authors: Department of Functional Brain Imaging Research, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba-shi, Chiba, 263-8555, Japan.
authors: Masaki
authors: M
authors: Tokunaga
authors: Department of Radiopharmaceutics Development, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba-shi, Chiba, 263-8555, Japan.
authors: Ming-Rong
authors: MR
authors: Zhang
authors: Department of Functional Brain Imaging Research, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba-shi, Chiba, 263-8555, Japan.
authors: Bin
authors: B
authors: Ji
authors: Department of Functional Brain Imaging Research, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba-shi, Chiba, 263-8555, Japan.
authors: Tetsuya
authors: T
authors: Suhara
authors: Department of Functional Brain Imaging Research, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba-shi, Chiba, 263-8555, Japan. higuchi.makoto@qst.go.jp.
authors: Makoto
authors: M
authors: Higuchi
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000686:Amyloidosis / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000276:immunology; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D007249:Inflammation / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000000981:diagnostic imaging* / Q000276:immunology; D010446:Peptide Fragments / Q000633:toxicity*; D049268:Positron-Emission Tomography / Q000379:methods; D011897:Random Allocation
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer’s disease; Beta amyloid; Cerebral metabolism; Neuroinflammation; Translocator protein