Neurochemical Research

, Volume 43, Issue 11, pp 2155–2164 | Cite as

Auricular Vagus Nerve Stimulation Exerts Antiinflammatory Effects and Immune Regulatory Function in a 6-OHDA Model of Parkinson’s Disease

  • Ying Jiang
  • Zhentang Cao
  • Huizi Ma
  • Guihong Wang
  • Xuemei Wang
  • Zhan Wang
  • Yaqin Yang
  • Huiqing Zhao
  • Genliang Liu
  • Longling LiEmail author
  • Tao FengEmail author
Original Paper


According to epidemiologic studies, smoking appears to downregulate the prevalence of Parkinson’s disease (PD), possibly due to antiinflammatory mechanisms via activation of α7 nicotinic acetylcholine receptors (α7 nAChRs). This receptor also appears to play a role in T-cell differentiation. Recently, it has become apparent that the innate immune system participates in PD pathogenesis. The aim of this study was to evaluate the effects of auricular vagus nerve stimulation (aVNS) on substantia nigra (SN) dopaminergic neurodegeneration and the associated neuroinflammation and immune responses in a rat PD model. Adult male Wistar rats were unilaterally administered 6-hydroxydopamine (6-OHDA) to the medial forebrain bundle, followed by aVNS treatment after surgery. Following motor behavioral tests, the expression of tyrosine hydroxylase (TH) in the SN and the levels of inflammatory cytokines in the ventral midbrain were evaluated. In addition, changes in the trends of subsets of CD4+ T lymphocytes in the SN were measured by immunofluorescence staining. Western blotting was used to evaluate the α7 nAChR protein level. Compared with 6-OHDA treats rats, aVNS treatment significantly improved motor deficits, increased TH and α7 nAChR expression, and reduced the levels of inflammatory cytokines (tumor necrosis factor-a (TNF-α) and interleukin-1β (IL-1β)) (p < 0.05). Additionally, aVNS increased the numbers of regulatory T (Treg) cells while decreasing T helper (Th)17 cells. aVNS exerted neuroprotective effects against dopaminergic damage, possibly by suppressing the evolution of inflammation and modulating innate immune responses. Thus, aVNS may be a potential promising therapy in the future.


Auricular vagus nerve stimulation α7 Nicotinic acetylcholine receptor Parkinson’s disease Th17 cells Treg cells 



Parkinson’s disease

α7 nAChRs

α7 Nicotinic acetylcholine receptors


Auricular vagus nerve stimulation


Substantia nigra




Tyrosine hydroxylase


Tumor necrosis factor-a




T helper






Vagus nerve stimulation


Food and drug administration


Medial forebrain bundle


Phosphate-buffered saline


Optimal cutting temperature


Substantia nigra pars compacta


Enzyme-linked immunosorbent assay


Foxhead boxp3


Retinoid-related orphan nuclear receptor γt


Sodium dodecyl sulfate-polyacrylamide gel electrophoresis


Standard error of the mean


One-way analysis of variance





This research was funded, in whole or in part, by funds from the Beijing Natural Science Foundation (No. 7174297), the National Natural Science Foundation of China (No. 31600724), and the Beijing Outstanding Talents Training Foundation (No. 2016000021469G210).

Compliance with Ethical Standards

Conflict of interest

No conflicts of interest exist in the submission of this manuscript.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Ying Jiang
    • 1
    • 2
    • 3
  • Zhentang Cao
    • 1
    • 2
    • 3
  • Huizi Ma
    • 1
    • 2
    • 3
  • Guihong Wang
    • 1
    • 2
    • 3
  • Xuemei Wang
    • 1
    • 2
    • 3
  • Zhan Wang
    • 1
    • 2
    • 3
  • Yaqin Yang
    • 1
    • 2
    • 3
  • Huiqing Zhao
    • 1
    • 2
    • 3
  • Genliang Liu
    • 1
    • 2
    • 3
  • Longling Li
    • 4
    Email author
  • Tao Feng
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Neurology, Center for Neurodegenerative Disease, Beijing Tiantan HospitalCapital Medical UniversityBeijingChina
  2. 2.Parkinson’s Disease CenterBeijing Institute for Brain DisordersBeijingChina
  3. 3.China National Clinical Research Center for Neurological DiseasesBeijingChina
  4. 4.Department of Neurology, Zhongshan HospitalXiamen UniversityXiamenChina

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