X-ray multiscale 3D neuroimaging to quantify cellular aging and neurodegeneration postmortem in a model of Alzheimer's disease.
Purpose : Modern neuroimaging lacks the tools necessary for whole-brain, anatomically dense neuronal damage screening. An ideal approach would include unbiased histopathologic identification of aging and neurodegenerative disease. Methods: We report the postmortem application of multiscale X-ray pha...
| Published in: | European Journal of Nuclear Medicine & Molecular Imaging Vol. 49; no. 13; pp. 4338 - 4358 |
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| Main Authors: | , , , , , , , , , , , , , |
| Format: | Journal Article |
| Published: |
Springer Nature
Nov2022
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=159866277&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 159866277 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 16197070 NPC jtl: European Journal of Nuclear Medicine & Molecular Imaging issn: 16197070 maglogo: N pubinfo: dt: Nov2022 vid: 49 iid: 13 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 159866277 10.1007/s00259-022-05896-5 159866277 ppf: 4338 ppct: 20 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: X-ray multiscale 3D neuroimaging to quantify cellular aging and neurodegeneration postmortem in a model of Alzheimer's disease. aug: au: Barbone, Giacomo E. Bravin, Alberto Mittone, Alberto Pacureanu, Alexandra Mascio, Giada Di Pietro, Paola Kraiger, Markus J. Eckermann, Marina Romano, Mariele Hrabě de Angelis, Martin Cloetens, Peter Bruno, Valeria Battaglia, Giuseppe Coan, Paola affil: Department of Medical Physics, Faculty of Physics, Ludwig-Maximilians-Universität München, Am Coulombwall 1, 85748, Garching, Germany sug: ab: Purpose : Modern neuroimaging lacks the tools necessary for whole-brain, anatomically dense neuronal damage screening. An ideal approach would include unbiased histopathologic identification of aging and neurodegenerative disease. Methods: We report the postmortem application of multiscale X-ray phase-contrast computed tomography (X-PCI-CT) for the label-free and dissection-free organ-level to intracellular-level 3D visualization of distinct single neurons and glia. In deep neuronal populations in the brain of aged wild-type and of 3xTgAD mice (a triply-transgenic model of Alzheimer's disease), we quantified intracellular hyperdensity, a manifestation of aging or neurodegeneration. Results: In 3xTgAD mice, the observed hyperdensity was identified as amyloid-β and hyper-phosphorylated tau protein deposits with calcium and iron involvement, by correlating the X-PCI-CT data to immunohistochemistry, X-ray fluorescence microscopy, high-field MRI, and TEM. As a proof-of-concept, X-PCI-CT was used to analyze hippocampal and cortical brain regions of 3xTgAD mice treated with LY379268, selective agonist of group II metabotropic glutamate receptors (mGlu2/3 receptors). Chronic pharmacologic activation of mGlu2/3 receptors significantly reduced the hyperdensity particle load in the ventral cortical regions of 3xTgAD mice, suggesting a neuroprotective effect with locoregional efficacy. Conclusions: This multiscale micro-to-nano 3D imaging method based on X-PCI-CT enabled identification and quantification of cellular and sub-cellular aging and neurodegeneration in deep neuronal and glial cell populations in a transgenic model of Alzheimer's disease. This approach quantified the localized and intracellular neuroprotective effects of pharmacological activation of mGlu2/3 receptors. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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