Objective: The main objective of the present study was to determine age and gender differences in measures of CAF in PLP-syn mice, a transgenic mouse model of MSA.

Background: Multiple system atrophy (MSA) is a rare and progressive neurodegenerative disorder. Cardiovascular autonomic failure (CAF) is one main clinical feature with significant impact on health-related quality of life. The neuropathological hallmark of MSA is the abnormal accumulation of alpha-synuclein (α-syn) in oligodendrocytes forming glial cytoplasmic inclusions. Only little is known about gender differences in CAF.

Method: A stable period of 5 min was used to perform all the analyses. Heart rate variability (HRV) was assessed in time (standard deviation normal to normal (SDNN) and root-mean square differences of successive R-R intervals (RMSSD)), frequential (low frequency power (LF) in normalized units (LFnu), high frequency power (HF) in normalized units (HFnu) and ratio between LF and HF (LF/HF)) and non-linear (standard deviation perpendicular (SD1) to and along (SD2) the line-of-identity) domains.  Atrioventricular conduction time (PQ interval), intraventricular conduction time (QRS complex), duration of ventricular depolarization and repolarization (QT / QTc intervals) were evaluated from the ECG signals. Baroreflex sensitivity (BRS) was estimated by the sequence method. The study was carried out in 6 and 12 months old transgenic PLP-syn and wild-type male and female mice. Three-way ANOVA (strain x gender x age) with Tukey’s method post-hoc was used to analyze data.

Results: A reduced overall variability and parasympathetic activity were observed at 6 and 12 months of age in PLP-syn male mice and at 12 months of age in PLP-syn female mice. The impaired HRV found in male would not worsen with age. Neither BRS nor ECG characteristics were significantly modified both in PLP-syn male and female mice with age.

Conclusion: Our results indicate an impaired HRV both in PLP-syn male and female mice indicating a CAF. However, it seems that the onset of CAF occurs later in PLP-syn female mice than PLP-syn male mice and that CAF is not exacerbated with age in PLP-syn male mice.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/age-and-gender-differences-in-cardiovascular-autonomic-failure-in-transgenic-plp-syn-mouse-model-of-multiple-system-atrophy/