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Sodium Butyrate Exacerbates Parkinson’s Disease by Aggravating Neuroinflammation and Colonic Inflammation in MPTP-Induced Mice Model

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Abstract

The abnormal production of short chain fatty acid (SCFAs) caused by gut microbial dysbiosis plays an important role in the pathogenesis and progression of Parkinson’s disease (PD). This study sought to evaluate how butyrate, one of SCFAs, affect the pathology in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) treated mouse model of PD. Sodium butyrate (NaB; 165 mg/kg/day i.g., 7 days) was administrated from the day after the last MPTP injection. Interestingly, NaB significantly aggravated MPTP-induced motor dysfunction (P < 0.01), decreased dopamine (P < 0.05) and 5-HT (P < 0.05) levels, exacerbated declines of dopaminergic neurons (34%, P < 0.05) and downregulated expression of tyrosine hydroxylase (TH, 47%, P < 0.05), potentiated glia-mediated neuroinflammation by increasing the number of microglia (17%, P < 0.05) and activating astrocytes (28%, P < 0.01). In vitro study also confirmed that NaB could significantly exacerbate pro-inflammatory cytokines expression (IL-1β, 4.11-fold, P < 0.01; IL-18, 3.42-fold, P < 0.01 and iNOS, 2.52-fold, P < 0.05) and NO production (1.55-fold, P < 0.001) in LPS-stimulated BV2 cells. In addition, NaB upregulated the expression of pro-inflammatory cytokines (IL-6, 3.52-fold, P < 0.05; IL-18, 1.72-fold, P < 0.001) and NLRP3 (3.11-fold, P < 0.001) in the colon of PD mice. However, NaB had no effect on NFκB, MyD88 and TNF-α expression in PD mice. Our results indicate that NaB exacerbates MPTP-induced PD by aggravating neuroinflammation and colonic inflammation independently of the NFκB/MyD88/TNF-α signaling pathway.

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Abbreviations

5-HT:

5-Hydroxytryptamine

CNS:

Central nervous system

DA:

Dopamine

FMT:

Fecal microbiota transplantation

GFAP:

Glial fibrillary acidic protein

HPLC:

High-performance liquid chromatography

Iba-1:

Ionized calcium-binding adaptor molecule 1

IF:

Immunofluorescence

IL-1β:

Interleukin-1 beta

IL-6:

Interleukin-6

IL-18:

Interleukin-18

iNOS:

Inductible nitric oxide synthase

MPTP:

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

NaB:

Sodium butyrate

NFκB:

Nuclear factor kappa B

NLRP3:

Nucleotide-binding oligomerization domain-like receptor protein 3

PBS:

Phosphate-buffered saline

PD:

Parkinson’s disease

qRT-PCR:

Quantitative real-time PCR

RRID:

Research resource identifier (see scicrunch.org)

SCFAs:

Short chain fatty acids

SN:

Substantia nigra pars compacta

TH:

Tyrosine hydroxylase

TNF-α:

Tumor necrosis factor alpha

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Acknowledgements

The authors acknowledge Dr. Stanley Li Lin from Shantou University for carefully revising the manuscript.

Funding

National Natural Science Foundation of China, No. 81771384 and No. 81801276; Public Health Research Center at Jiangnan University, No. JUPH201801; Chinese postdoctoral science foundation, No. 2018M630512.

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Author notes

  1. Chen-Meng Qiao, Meng-Fei Sun and Xue-Bing Jia have contributed equally to this study.

Authors and Affiliations

  1. Public Health Research Center at Jiangnan University, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, China

    Chen-Meng Qiao, Meng-Fei Sun, Xue-Bing Jia, Yang Li, Bo-Ping Zhang, Li-Ping Zhao, Yun Shi, Zhi-Lan Zhou, Ying-Li Zhu, Chun Cui & Yan-Qin Shen

  2. School of Food Science and Technology, Jiangnan University, Wuxi, 214122, Jiangsu, China

    Chen-Meng Qiao

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  1. Chen-Meng Qiao
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Qiao, CM., Sun, MF., Jia, XB. et al. Sodium Butyrate Exacerbates Parkinson’s Disease by Aggravating Neuroinflammation and Colonic Inflammation in MPTP-Induced Mice Model. Neurochem Res 45, 2128–2142 (2020). https://doi.org/10.1007/s11064-020-03074-3

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