Disruption of afferent neural circuits leads to arrhythmia in the animal model of hereditary sensory and autonomic neuropathy 6.

Abstract

Hereditary sensory and autonomic neuropathies (HSANs) are a group of recessive genetic disorders affecting the sensory and autonomic components of the peripheral nervous system (PNS). Compared with somatosensory dysfunctions, the pathogenesis of visceral dysfunction in HSANs remains understudied. This study investigated the neural circuit mechanisms underlying the arrhythmias observed in conditional Dystonin () gene-trap mice, an animal model of HSAN type VI (HSAN-VI) in which Cre recombinase inactivatesexpression in selective neural circuits. Inactivation of thegene in PNS neurons usingcaused the degeneration of sensory and sympathetic ganglionic neurons. This was accompanied by arrhythmia, characterized by increased heart rate variability and irregular pulse frequency, which was prominent under isoflurane anesthesia and occurred in the absence of protein aggregate cardiomyopathy. Furthermore, selective inactivation of thegene in PNS sensory neurons usingresulted in similar dysregulation of cardiac rhythm. These findings suggest that arrhythmias caused bymutations arise from the disruption of visceral afferent circuits, and that these neural circuits could be potential therapeutic targets for visceral dysfunction in HSAN-VI.