Barbone, G.E.* ; Bravin, A.* ; Mittone, A.* ; Pacureanu, A.* ; Mascio, G.* ; Di Pietro, P.* ; Kraiger, M. ; Eckermann, M.* ; Romano, M.* ; Hrabě de Angelis, M. ; Cloetens, P.* ; Bruno, V.* ; Battaglia, G.* ; Coan, P.*
X-ray multiscale 3D neuroimaging to quantify cellular aging and neurodegeneration postmortem in a model of Alzheimer’s disease.
Eur. J. Nucl. Med. Mol. Imaging 49, 4338-4357 (2022)
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Alzheimer’s Disease ; Metabotropic Glutamate Receptors ; Micro-ct ; Nano-imaging ; Neuro-radiology ; Neurodegeneration
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2022
Prepublished im Jahr
HGF-Berichtsjahr
2022
ISSN (print) / ISBN
1619-7070
e-ISSN
1432-105X
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 49,
Heft: 13,
Seiten: 4338-4357
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Springer
Verlagsort
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30201 - Metabolic Health
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-500692-001
G-500600-001
Förderungen
Région Auvergne-Rhône-Alpes
Fondation pour la Recherche Medicale
Ministero della Salute
Bundesministerium für Bildung und Forschung
Deutsche Forschungsgemeinschaft
European Cooperation in Science and Technology
International Max Plank Research School of Advanced Photon Science
GIS-IBISA
Fonds FEDER
DFG Cluster of Excellence)—Munich Center for Advanced Photonics
Copyright
Erfassungsdatum
2022-07-28