Transcutaneous auricular vagal nerve stimulation alleviated the development of peripheral and central symptoms of systemic lupus erythematosus in MRL/lpr mice

Abstract Objective. The objective of this study was to investigate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on the development of peripheral and central symptoms of systemic lupus erythematosus (SLE) in MRL/lpr mice. Methods. MRL/lpr mice were treated with taVNS for ten weeks, and the severity of both the central and peripheric symptoms was assessed. Results. taVNS activated tyrosine hydroxylase positive (TH + ) neurons in the locus coeruleus (LC), improved cognitive impairment, and alleviated depression-like behaviors. taVNS reduced the number of hippocampal microglia and protected the LC TH + neurons in MRL/lpr mice. Treatment with taVNS also retarded the development of lymphadenectasis and splenomegaly, decreased the proportion of double-negative T (DNT) cells, as well as alleviated nephritis and renal IgG deposition in MRL/lpr mice. However, when the LC TH + neurons were selectively lesioned, both peripheral and central therapeutic action of taVNS was eliminated. Finally, the results of liquid chromatography-tandem mass spectrometry (LC-MS) indicated taVNS mainly LC-dependently reduced the concentration of norepinephrine and adrenaline in serum. Conclusion. This study provides direct evidence that taVNS can retard the development of peripheral and central symptoms of SLE, which may be related to its modulating the activity of LC TH + neurons. Our findings suggest that taVNS may be a potential non-invasive treatment approach for SLE, although further research is needed to explore its clinical applications in human patients.