| First Author | Rosales Jubal E | Year | 2021 |
| Journal | Sci Rep | Volume | 11 |
| Issue | 1 | Pages | 6649 |
| PubMed ID | 33758244 | Mgi Jnum | J:304922 |
| Mgi Id | MGI:6695597 | Doi | 10.1038/s41598-021-85912-0 |
| Citation | Rosales Jubal E, et al. (2021) Acitretin reverses early functional network degradation in a mouse model of familial Alzheimer's disease. Sci Rep 11(1):6649 |
| abstractText | 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. |
