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Age and Gender Differences in Cardiovascular Autonomic Failure in the Transgenic PLP-syn Mouse, a Model of Multiple
Marc Kermorgant1,2, Pierre-Olivier Fernagut3,4, Wassilios G Meissner3,5,6,7
1INSERM DR Midi-Pyrénées Limousin, Institute of Cardiovascular and Metabolic Diseases (I2MC) UMR1297, University Hospital of Toulouse, Toulouse, France.
This study reveals that female mice with a genetic predisposition to Multiple System Atrophy (MSA) exhibit impaired heart rate variability (HRV), indicating autonomic failure (AF). These cardiovascular changes were age-dependent and specific to females, unlike their male counterparts.
Area of Science:
- Neuroscience
- Cardiovascular Physiology
- Genetics
Background:
- Multiple system atrophy (MSA) is a rare neurodegenerative disease characterized by autonomic failure (AF).
- The neuropathological hallmark of MSA involves α-synuclein accumulation in oligodendrocytes.
- Limited understanding exists regarding gender and age-specific differences in AF within MSA.
Purpose of the Study:
- To investigate gender and age-related differences in autonomic function in a transgenic mouse model of MSA.
- To assess cardiovascular autonomic function in PLP-α-syn mice compared to wild-type (WT) controls.
Main Methods:
- Evaluated heart rate variability (HRV) in time, frequency, and non-linear domains.
- Assessed baroreflex sensitivity (BRS) using the sequence method.
- Measured QT/QTc intervals from ECG signals in 6 and 12-month-old male and female transgenic PLP-α-syn and WT mice.
- Utilized three-way ANOVA for data analysis.
Main Results:
- Baroreflex sensitivity (BRS) was significantly altered in PLP-α-syn mice in an age-dependent manner.
- No significant modifications were observed in QT and QTc intervals.
- Impaired HRV was evident in 12-month-old female PLP-α-syn mice, but not in males, suggesting cardiovascular autonomic dysfunction.
Conclusions:
- Cardiovascular autonomic dysfunction, specifically impaired HRV, is present in female transgenic mice modeling MSA.
- These findings highlight potential gender and age-specific differences in the manifestation of autonomic failure in MSA.
- The study provides insights into the pathophysiology of AF in MSA using a genetic mouse model.
