| Abstrakt: |
Key points The present study provides evidence that the cardiomyopathy observed in spinal muscular atrophy (SMA) model mice is mainly due to intrinsic cardiac alteration but not to autonomic impairment., We demonstrated a non-pathological sympathetic activity on the heart of type 2 SMA-like mice, which likely counteracts the dramatic alteration of the cardiac function, such as arrhythmia and reduced heart rate., We demonstrated for the first time that physical exercise partially restores cardiac conduction efficiency, prevents fibrosis, attenuates defects in protein expression, bradycardia and arrhythmias leading to the partial recovery of heart and respiratory rates in exercised SMA-like mice., This study indicates a profound involvement of cellular, structural and vascular cardiac dysfunction in the pathogenesis of SMA, widely opening alternative pharmacological and non-pharmacological therapeutic strategies that would most certainly include physical exercise., Abstract Spinal muscular atrophy (SMA), the leading genetic cause of death in infants worldwide, is due to the misexpression of the survival of motor neuron protein, causing death of motor neurons. Several clinical symptoms suggested that, in addition to motor neurons, the autonomic nervous systems could be implicated in the cardiac function alterations observed in patienst with SMA. These alterations were also found in a severe SMA mouse model, including bradycardia and a reduction of sympathetic innervation, both associated with autonomic imbalance. In the present study, we investigate the extent of autonomic dysfunction and the effects of a running-based exercise on the altered cardiorespiratory function in type 2 SMA-like mice. We observed that the SMA induced: (1) a dramatic alteration of intrinsic cardiac conduction associated with bradycardia; (2) a severe cardiomyopathy associated with extensive ventricular fibrosis; and (3) a delay in cardiac muscle maturation associated with contractile protein expression defects. Furthermore, our data indicate that the sympathetic system is not only functioning, but also likely contributes to alleviate the bradycardia and the arrhythmia in SMA-like mice. Moreover, physical exercise provides many benefits, including the reduction of cardiac protein expression defect, the reduction of fibrosis, the increase in cardiac electrical conduction velocity, and the drastic reduction in bradycardia and arrhythmias resulting in the partial restoration of the cardiac function in these mice. Thus, modulating the cardiorespiratory function in SMA could represent a new target for improving supportive care and for developing new pharmacological and non-pharmacological interventions that would most certainly include physical exercise. [ABSTRACT FROM AUTHOR] |
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