Journal Article

DZNE-2023-01166

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Fragmentation of functional resting state brain networks in a transgenic mouse model of tau pathology: A metabolic connectivity study using [18F]FDG-PET

Endepols, H. ; Anglada-Huguet, M.DZNE* ; Mandelkow, E.DZNE* ; Neumaier, B. ; Mandelkow, E. M.DZNE* ; Drzezga, A. (Last author)DZNE*

2024
Academic Press Orlando, Fla.

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Please use a persistent id in citations: doi:10.1016/j.expneurol.2023.114632

Abstract: In a previous study, regional reductions in cerebral glucose metabolism have been demonstrated in the tauopathy mouse model rTg4510 (Endepols et al., 2022). Notably, glucose hypometabolism was present in some brain regions without co-localized synaptic degeneration measured with [18F]UCB-H. We hypothesized that in those regions hypometabolism may reflect reduced functional connectivity rather than synaptic damage. To test this hypothesis, we performed seed-based metabolic connectivity analyses using [18F]FDG-PET data in this mouse model. Eight rTg4510 mice at the age of seven months and 8 non-transgenic littermates were injected intraperitoneally with 11.1 ± 0.8 MBq [18F]FDG and spent a 35-min uptake period awake in single cages. Subsequently, they were anesthetized and measured in a small animal PET scanner for 30 min. Three seed-based connectivity analyses were performed per group. Seeds were selected for apparent mismatch between [18F]FDG and [18F]UCB-H. A seed was placed either in the medial orbitofrontal cortex, dorsal hippocampus or dorsal thalamus, and correlated with all other voxels of the brain across animals. In the control group, the emerging correlative pattern was strongly overlapping for all three seed locations, indicating a uniform fronto-thalamo-hippocampal resting state network. In contrast, rTg4510 mice showed three distinct networks with minimal overlap. Frontal and thalamic networks were greatly diminished. The hippocampus, however, formed a new network with the whole parietal cortex. We conclude that resting-state functional networks are fragmented in the brain of rTg4510 mice. Thus, hypometabolism can be explained by reduced functional connectivity of brain areas devoid of tau-related pathology, such as the thalamus.

Keyword(s): Animals (MeSH) ; Mice (MeSH) ; Fluorodeoxyglucose F18: metabolism (MeSH) ; Mice, Transgenic (MeSH) ; Positron-Emission Tomography (MeSH) ; Brain: metabolism (MeSH) ; Brain Mapping (MeSH) ; Disease Models, Animal (MeSH) ; Magnetic Resonance Imaging (MeSH) ; Metabolic connectivity ; Small animal PET ; Tauopathy mouse model ; Fluorodeoxyglucose F18

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Contributing Institute(s):

1. Positron Emissions Tomography (PET) (AG Boecker)
2. Translational Dementia Research (Bonn) (AG Schneider)
3. Cell and Animal Models of Neurodegeneration (AG Mandelkow 2)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2024

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Database coverage:
; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Web of Science Core Collection

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