biostudies-literatureUnknown11(1)Rosales Jubal EStiftung Rheinland-Pfalz für InnovationBoehringer Ingelheim FoundationFocus Program Translational NeurosciencesAlfred Dollwet FoundationUniversitätsmedizin der Johannes Gutenberg-Universität MainzAberrant 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.Scientific reports6649https://www.ebi.ac.uk/biostudies/studies/S-EPMC7988040biostudies-literatureAcitretin reverses early functional network degradation in a mouse model of familial Alzheimer's disease.PMC7988040Wierczeiko ASchmitt UDos Santos Guilherme MTose AEndres KSchuck FRosales Jubal ESchmeisser MJRoesler MKReinhardt SRuffini NSchwalm MBarger ZStroh AfalseAcitretin reverses early functional network degradation in a mouse model of familial Alzheimer's disease.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.2021-01-01T00:00:00Z2021 Mar2025-04-18T21:43:28.234Z2025-04-07T09:34:14.593ZS-EPMC79880403375824410.1038/s41598-021-85912-0