Frontiers in Neurology (Jun 2022)

Age and Gender Differences in Cardiovascular Autonomic Failure in the Transgenic PLP-syn Mouse, a Model of Multiple System Atrophy

  • Marc Kermorgant,
  • Marc Kermorgant,
  • Pierre-Olivier Fernagut,
  • Pierre-Olivier Fernagut,
  • Wassilios G. Meissner,
  • Wassilios G. Meissner,
  • Wassilios G. Meissner,
  • Wassilios G. Meissner,
  • Dina N. Arvanitis,
  • Du N'Guyen,
  • Jean-Michel Senard,
  • Jean-Michel Senard,
  • Anne Pavy-Le Traon,
  • Anne Pavy-Le Traon

DOI
https://doi.org/10.3389/fneur.2022.874155
Journal volume & issue
Vol. 13

Abstract

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Multiple system atrophy (MSA) is a rare and progressive neurodegenerative disorder. Autonomic failure (AF) is one main clinical feature which has a significant impact on health-related quality of life. The neuropathological hallmark of MSA is the abnormal accumulation of α-synuclein in oligodendrocytes forming glial cytoplasmic inclusions. Only little is known about gender and age differences in AF in MSA. This study was carried out in 6 and 12 months old transgenic PLP-α-syn and WT male and female mice. Heart rate variability (HRV) was assessed both in time, frequential and non-linear domains. Baroreflex sensitivity (BRS) was estimated by the sequence method. Duration of ventricular depolarization and repolarization (QT/QTc intervals) were evaluated from the ECG signals. Three-way ANOVA (genotype x gender x age) with Sidak's method post-hoc was used to analyze data. BRS was significantly changed in PLP-α-syn mice and was age-dependent. QT and QTc intervals were not significantly modified in PLP-α-syn mice. An impaired HRV was observed at 12 months of age in PLP-α-syn female but not in male mice, indicative of cardiovascular AF.

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