Acitretin reverses early functional network degradation in a mouse model of familial Alzheimer's disease.

  • Competence Center for Methodology and Statistics
March 23, 2021 By:
  • Rosales Jubal E
  • Schwalm M
  • Dos Santos Guilherme M
  • Schuck F
  • Reinhardt S
  • Tose A
  • Barger Z
  • Roesler MK
  • Ruffini N
  • Wierczeiko A
  • Schmeisser MJ
  • Schmitt U
  • Endres K
  • Stroh A.

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 Mar. Sci Rep.11(1):6649.
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