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Authors: Rosales Jubal, Eduardo
Schwalm, Miriam
Santos Guilherme, Malena dos
Schuck, Florian
Reinhardt, Sven
Tose, Amanda
Barger, Zeke
Roesler, Mona K.
Ruffini, Nicolas
Wierczeiko, Anna
Schmeisser, Michael J.
Schmitt, Ulrich
Endres, Kristina
Stroh, Albrecht
Title: Acitretin reverses early functional network degradation in a mouse model of familial Alzheimer’s disease
Online publication date: 20-Sep-2021
Language: english
Abstract: Aberrant activity of local functional networks underlies memory and cognition deficits in Alzheimer’s disease (AD). Hyperactivity was observed in microcircuits of mice AD-models showing plaques, and also recently in early stage AD mutants prior to amyloid deposition. However, early functional effects of AD on cortical microcircuits remain unresolved. Using two-photon calcium imaging, we found altered temporal distributions (burstiness) in the spontaneous activity of layer II/III visual cortex neurons, in a mouse model of familial Alzheimer’s disease (5xFAD), before plaque formation. Graph theory (GT) measures revealed a distinct network topology of 5xFAD microcircuits, as compared to healthy controls, suggesting degradation of parameters related to network robustness. After treatment with acitretin, we observed a re-balancing of those network measures in 5xFAD mice; particularly in the mean degree distribution, related to network development and resilience, and post-treatment values resembled those of age-matched controls. Further, behavioral deficits, and the increase of excitatory synapse numbers in layer II/III were reversed after treatment. GT is widely applied for whole-brain network analysis in human neuroimaging, we here demonstrate the translational value of GT as a multi-level tool, to probe networks at different levels in order to assess treatments, explore mechanisms, and contribute to early diagnosis.
DDC: 610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
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Journal: Scientific reports
Pages or article number: 6649
Publisher: Macmillan Publishers Limited, part of Springer Nature
Publisher place: London
Issue date: 2021
ISSN: 2045-2322
Publisher URL:
Publisher DOI: 10.1038/s41598-021-85912-0
Appears in collections:JGU-Publikationen

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