Autoren:	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
Titel:	Acitretin reverses early functional network degradation in a mouse model of familial Alzheimer’s disease
Online-Publikationsdatum:	20-Sep-2021
Erscheinungsdatum:	2021
Sprache des Dokuments:	Englisch
Zusammenfassung/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-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-6354
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	Scientific reports 11
Seitenzahl oder Artikelnummer:	6649
Verlag:	Macmillan Publishers Limited, part of Springer Nature
Verlagsort:	London
Erscheinungsdatum:	2021
ISSN:	2045-2322
URL der Originalveröffentlichung:	https://doi.org/10.1038/s41598-021-85912-0
DOI der Originalveröffentlichung:	10.1038/s41598-021-85912-0
Enthalten in den Sammlungen:	JGU-Publikationen