Locus coeruleus tyrosine hydroxylase positive neurons mediated the peripheral and central therapeutic effects of transcutaneous auricular vagus nerve stimulation (taVNS) in MRL/lpr mice

  • Brain Stimul. 2023 Dec 23;17(1):49-64. doi: 10.1016/j.brs.2023.12.008.
Hongjie Lv  1 ,  Xiu Yu  1 ,  Ping Wang  2 ,  Mengxian Luo  1 ,  Yijun Luo  1 ,  Haimei Lu  1 ,  Keer Wang  1 ,  Anran Xi  1 ,  Chengping Wen  3 ,  Zhenghao Xu  4
Affiliations
  • 1. Laboratory of Rheumatology & Institute of TCM Clinical Basic Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China; Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
  • 2. Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
  • 3. Laboratory of Rheumatology & Institute of TCM Clinical Basic Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China; Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China. Electronic address: [email protected].
  • 4. Laboratory of Rheumatology & Institute of TCM Clinical Basic Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China; Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China; Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China. Electronic address: [email protected].
PMID: 38145753 DOI: 10.1016/j.brs.2023.12.008
Abstract

Objective: This study aims to investigate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on the development of systemic lupus erythematosus (SLE) in MRL/lpr mice.

Methods: MRL/lpr mice were treated with taVNS for ten weeks. Locus coeruleus (LC) Tyrosine Hydroxylase positive (TH+) neurons were selectively lesioned by stereotactic injection of 6-hydroxydopamine (6-OHDA) or selectively activated by chemogenetic methods. Sympathetic denervation was conducted by intraperitoneal injection of 6-OHDA.

Results: TaVNS activated the TH + neurons in LC. TaVNS produced central therapeutic effects by reducing the number of hippocampal microglia, and increasing the number of surviving LC TH+ neurons in MRL/lpr mice. TaVNS also retarded the development of lymphadenectasis and splenomegaly, decreased the proportion of double-negative T (DNT) cells, and alleviated nephritis in MRL/lpr mice. The lesion of LC TH+ neurons eliminated both these central and peripheral therapeutic effects of taVNS, while chemogenetic activation of LC TH+ neurons mimicked most central and peripheral protective effects of taVNS in MRL/lpr mice. Furthermore, taVNS regulated the autonomic nervous system in MRL/lpr mice.

Conclusion: This study provides direct evidence that taVNS can retard the development of peripheral and central symptoms of SLE, which is mediated by the LC TH+ neurons.

Keywords
Locus coeruleus; Systemic lupus erythematosus; Transcutaneous auricular vagus nerve stimulation; Vagus nerve stimulation.
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