Sympathetic Controls Fate and Function of Adult Sensory Neurons

Abstract Sensory neurons in the dorsal root ganglia (DRG) serve as conduits for transmitting peripheral stimuli to the central nervous system, playing an essential role in sensory perception and coordinated movement. This study reveals that sympathetic innervation is critical for these neurons’ survival and functional integrity. Using a surgical microsympathectomy model in mice, we found that targeted sympathetic denervation of the lumbar DRGs triggered robust neuronal death, peaking four days post-surgery. This cellular loss is evidenced by reduced spinal projections, decreased nerve density in the skin, and impaired sensory and motor functions. We further identified norepinephrine (NE) as a vital neuroprotective agent; continuous NE supplementation effectively prevented cell death. Additionally, macrophage activation following denervation proved protective, as macrophage depletion exacerbated neuronal loss. It is suggested that the loss of sympathetic input disrupted mitochondrial homeostasis, releasing Smac/DIABLO, activating Caspase-3, and leading to cell death. These findings highlight the sympathetic nervous system’s novel role in maintaining sensory neuron viability through tonic adrenergic support. Competing Interest Statement The authors have declared no competing interest.