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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 Li
  • Tao Feng
Original Paper
  • 47 Downloads

Abstract

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.

Keywords

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

Abbreviations

PD

Parkinson’s disease

α7 nAChRs

α7 Nicotinic acetylcholine receptors

aVNS

Auricular vagus nerve stimulation

SN

Substantia nigra

6-OHDA

6-Hydroxydopamine

TH

Tyrosine hydroxylase

TNF-α

Tumor necrosis factor-a

IL-1β

Interleukin-1β

Th

T helper

Treg

Regulatory

MPTP

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

VNS

Vagus nerve stimulation

FDA

Food and drug administration

MFB

Medial forebrain bundle

PBS

Phosphate-buffered saline

OCT

Optimal cutting temperature

SNc

Substantia nigra pars compacta

ELISA

Enzyme-linked immunosorbent assay

Foxp3

Foxhead boxp3

RORγt

Retinoid-related orphan nuclear receptor γt

SDS-PAGE

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis

SEM

Standard error of the mean

ANOVA

One-way analysis of variance

Ach

Acetylcholine

Notes

Acknowledgements

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
  • Tao Feng
    • 1
    • 2
    • 3
  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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