Key result
In male rats with experimental peripheral artery disease, NGF increased ASIC3 currents in muscle dorsal root ganglion neurons via JNK and NF-κB signaling pathways.
Why the study?
The mechanisms driving exaggerated autonomic and exercise pressor reflex responses in peripheral artery disease, specifically whether NGF signaling contributes to dorsal root ganglion ASIC activity, remain undetermined.
NGF signaling via JNK and NF-κB pathways increases ASIC3 activity in DRG neurons, providing a potential mechanism for the exaggerated exercise pressor reflex in peripheral artery disease.
A feature of peripheral artery diseases (PAD) includes limb ischemia/reperfusion (I/R) and ischemia. Both I/R and ischemia amplify muscle afferent nerve‐activated reflex sympathetic nervous and blood pressure responses (termed as exercise pressor reflex). Nevertheless, the underlying mechanisms responsible for the exaggerated autonomic responses in PAD are undetermined. Previous studies suggest that acid‐sensing ion channels (ASICs) in muscle dorsal root ganglion (DRG) play a leading role in regulating the exercise pressor reflex in PAD. Thus, we determined if signaling pathways of nerve growth factor (NGF) contribute to the activities of ASICs in muscle DRG neurons of PAD. In particular, we examined ASIC1a and ASIC3 currents in isolectin B 4 ‐negative muscle DRG neurons, a distinct subpopulation depending on NGF for survival. Hindlimb I/R and ischemia were obtained in male rats. In results, femoral artery occlusion increased the levels of NGF and NGF‐stimulated TrkA receptor in DRGs, whereas they led to upregulation of ASIC3 but not ASIC1a. In addition, application of NGF onto DRG neurons increased the density of ASIC3 currents and the effect of NGF was significantly attenuated by TrkA antagonist GW441756. Moreover, the enhancing effect of NGF on the density of ASIC3‐like currents was decreased by the respective inhibition of intracellular signaling pathways, namely JNK and NF‐κB, by antagonists SP600125 and PDTC. Our results suggest contribution of NGF to the activities of ASIC3 currents via JNK and NF‐κB signaling pathways in association with the exercise pressor reflex in experimental PAD.
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Li et al. (2024) studied Experimental peripheral artery disease. NGF application and signaling pathway antagonists was evaluated on ASIC3 current density and upregulation. In male rats with experimental peripheral artery disease, NGF increased ASIC3 currents in muscle dorsal root ganglion neurons via JNK and NF-κB signaling pathways.
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