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Brain energy metabolism and neuroinflammation in ageing APP/PS1-21 mice using longitudinal ¹⁸F-FDG and ¹⁸F-DPA-714 PET imaging.

ABSTRACT: Preclinical animal model studies of brain energy metabolism and neuroinflammation in Alzheimer's disease have produced conflicting results, hampering both the elucidation of the underlying disease mechanism and the development of effective Alzheimer's disease therapies. Here, we aimed to quantify the relationship between brain energy metabolism and neuroinflammation in the APP/PS1-21 transgenic mouse model of Alzheimer's disease using longitudinal in vivo¹⁸F-FDG and ¹⁸F-DPA-714) PET imaging and ex vivo brain autoradiography. APP/PS1-21 (TG, n?=?9) and wild type control mice (WT, n?=?9) were studied longitudinally every third month from age 6 to 15 months with ¹⁸F-FDG and ¹⁸F-DPA-714 with a one-week interval between the scans. Additional TG (n?=?52) and WT (n?=?29) mice were used for ex vivo studies. In vivo, the ¹⁸F-FDG SUVs were lower and the ¹⁸F-DPA-714 binding ratios relative to the cerebellum were higher in the TG mouse cortex and hippocampus than in WT mice at age 12 to 15 months ( p?18F-DPA-714 studies but not the ¹⁸F-FDG studies. This longitudinal PET study demonstrated decreased energy metabolism and increased inflammation in the brains of APP/PS1-21 mice compared to WT mice.

SUBMITTER: Takkinen JS

PROVIDER: S-EPMC5536795 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Brain energy metabolism and neuroinflammation in ageing APP/PS1-21 mice using longitudinal 18F-FDG and 18F-DPA-714 PET imaging.

Takkinen Jatta S JS López-Picón Francisco R FR Al Majidi Rana R Eskola Olli O Krzyczmonik Anna A Keller Thomas T Löyttyniemi Eliisa E Solin Olof O Rinne Juha O JO Haaparanta-Solin Merja M

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20160101 8

Preclinical animal model studies of brain energy metabolism and neuroinflammation in Alzheimer's disease have produced conflicting results, hampering both the elucidation of the underlying disease mechanism and the development of effective Alzheimer's disease therapies. Here, we aimed to quantify the relationship between brain energy metabolism and neuroinflammation in the APP/PS1-21 transgenic mouse model of Alzheimer's disease using longitudinal in vivo18F-FDG and 18F-DPA ...[more]

PMID: 27834284

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Project description:Hypothyroidism is closely related to mental disorders, mainly depression, through an as-yet-unknown mechanism. The cerebral inflammatory immune process has been implied to play a pivotal role in the onset of affective symptoms in several conditions. In order to gain insight into the mechanism underlying the depressive behaviors in hypothyroid rats, brain microglial activation was evaluated using micro positron emission tomography imaging with a translocator protein (TSPO) radioligand. Hypothyroidism was induced in adult male Wistar rats by administration of 0.05% propylthiouracil in drinking water for five weeks. Open field, forced swimming and tail suspension tests were employed to evaluate the depressive behavior in hypothyroid rats, and the relationship between the behavioral changes and brain microglial activation was evaluated using [18F] DPA-714 micro positron emission tomography imaging. The open field test revealed significantly reduced first-minute activity and rearing behavior in the hypothyroid group, as well as significantly increased immobility in the forced swimming test and the tail suspension test. Hypothyroidism induced significantly increased microglial activation in the hippocampus. The radioligand uptake in the hippocampus correlated negatively with first-minute activity in the open field test (p < 0.05), and the radioligand uptake in the hippocampus correlated positively with changes in the immobility time in the forced swimming test and the tail suspension test (p < 0.05). Immunohistochemistry also confirmed the activation of microglia and inflammatory bodies in hypothyroid rats. The results indicate that hypothyroidism can induce depressive behavior in adult Wistar rats, microglial activation in the hippocampus plays an important role in the depressive behavior in hypothyroid rats and the inflammatory immune mechanism may underlie the behavioral abnormalities in thyroid dysfunction. Furthermore, the findings in the present study suggest there might be a common mechanism underlying depressive behavior in adult-onset hypothyroidism and depression.

Dataset Information

Brain energy metabolism and neuroinflammation in ageing APP/PS1-21 mice using longitudinal ¹⁸F-FDG and ¹⁸F-DPA-714 PET imaging.

Publications

Brain energy metabolism and neuroinflammation in ageing APP/PS1-21 mice using longitudinal <sup>18</sup>F-FDG and <sup>18</sup>F-DPA-714 PET imaging.

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