Kermorgant Marc, Fernagut Pierre-Olivier, Meissner Wassilios G, Arvanitis Dina N, N'Guyen Du, Senard Jean-Michel, Pavy-Le Traon Anne
INSERM DR Midi-Pyrénées Limousin, Institute of Cardiovascular and Metabolic Diseases (I2MC) UMR1297, University Hospital of Toulouse, Toulouse, France.
French Reference Center for Multiple System Atrophy, Neurology Department, University Hospital of Toulouse, Toulouse, France.
Front Neurol. 2022 Jun 2;13:874155. doi: 10.3389/fneur.2022.874155. eCollection 2022.
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 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.
多系统萎缩（MSA）是一种罕见的进行性神经退行性疾病。自主神经功能衰竭（AF）是其主要临床特征之一，对健康相关生活质量有重大影响。MSA的神经病理学标志是α-突触核蛋白在少突胶质细胞中异常积聚，形成胶质细胞质包涵体。关于MSA中AF的性别和年龄差异，人们了解甚少。本研究在6个月和12个月大的转基因PLP-α-突触核蛋白和野生型雄性及雌性小鼠中进行。从时域、频域和非线性域评估心率变异性（HRV）。通过序列法估计压力反射敏感性（BRS）。从心电图信号评估心室去极化和复极化的持续时间（QT/QTc间期）。采用带有Sidak法的三因素方差分析（基因型×性别×年龄）来分析数据。PLP-α-突触核蛋白小鼠的BRS有显著变化，且与年龄相关。PLP-α-突触核蛋白小鼠的QT和QTc间期无显著改变。在12个月大时，PLP-α-突触核蛋白雌性小鼠而非雄性小鼠观察到HRV受损，提示心血管自主神经功能衰竭。
