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Neurotoxicity Research

, Volume 35, Issue 4, pp 918–930 | Cite as

Local Gastrointestinal Injury Exacerbates Inflammation and Dopaminergic Cell Death in Parkinsonian Mice

  • Ana-Luisa Gil-Martínez
  • Cristina Estrada
  • Lorena Cuenca
  • Juan-Antonio Cano
  • Manuel Valiente
  • Carlos-Manuel Martínez-Cáceres
  • Emiliano Fernández-Villalba
  • María-Trinidad HerreroEmail author
Original Article

Abstract

The cause of progressive degeneration in Parkinson’s disease is not clear, although, in the last years, different studies have suggested that both brain and peripheral inflammation could play a key role in the progression of this disorder. In our study, we aimed to analyze the effect of an acute inflammation confined to the colon on dopaminergic neuronal death and glial response in mice intoxicated with MPTP. The results obtained show a very significant decrease of dopaminergic neurons in the SNpc as well as a significant decrease of dopaminergic fibers in the striatum of the MPTP+DSS-treated group compared with the control animals. In addition, there was a significant exacerbation of microglial and astrocytes activation in MPTP+DSS animals compared with the control group. This data suggests that a specific gastrointestinal injury, which induces a systemic inflammatory response, is able to exacerbate cell death mechanisms of the remaining dopaminergic neurons and then contributes to the persistent progression of the disease. These results leave open new lines of research on the role of exclusive colonic inflammation and the progression of nigrostriatal dopaminergic degeneration.

Keywords

Parkinson’s disease Ulcerative colitis Systemic inflammation Neurodegeneration 

Abbreviations

DAB

3,3′-Diaminobenzidine

DAI

Disease activity index

DSS

Dextran sodium sulfate

GFAP

Glial fibrillary acidic protein

LPS

Lipopolysaccharide

LRRK2

Leucine-rich repeat kinase 2

MPTP

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

NO

Nitric oxide

ROS

Reactive oxygen species

SNpc

Substantia nigra pars compacta

TH

Tyrosine hydroxylase

Notes

Acknowledgments

Research work of the authors was supported by the Spanish Ministry of Science and Innovation (FIS PI13 01293), Fundación Séneca (19540/PI/14) and “Prediction of cognitive properties of new drug candidates for neurodegenerative diseases in early clinical development” (European Community’s Seventh Framework Programme (FP7/2007-2013) for the Innovative Medicine Initiative under Grant Agreement No 115009) to MTH.

Author Contributions

MTH designed the research; ALGM and CE performed the research and analyzed the data; JAC, MV, CMMC, and EFV contributed to the care of the animals and histological quantifications; LC discussed the in vivo results; ALGM and MTH discussed all the results and wrote the paper.

Compliance with Ethical Standards

All procedures related to animal maintenance, care and experimentation were carried out in accordance with the European Community Council Directive (2010/63/UE) for animals to be used in preclinical studies and were approved by the Institutional Committee on Animal Ethics of the University of Murcia (REGA ES300305440012).

Conflicts of Interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ana-Luisa Gil-Martínez
    • 1
    • 2
  • Cristina Estrada
    • 1
    • 2
  • Lorena Cuenca
    • 1
    • 2
  • Juan-Antonio Cano
    • 1
  • Manuel Valiente
    • 1
  • Carlos-Manuel Martínez-Cáceres
    • 3
  • Emiliano Fernández-Villalba
    • 1
    • 2
  • María-Trinidad Herrero
    • 1
    • 2
    Email author
  1. 1.Clinical and Experimental Neuroscience Group (NiCE-IMIB), Department of Human Anatomy and Psychobiology, Institute for Aging Research, School of MedicineUniversity of MurciaMurciaSpain
  2. 2.Biomedical Research Institute of Murcia (IMIB-Arrixaca), Campus of Health SciencesUniversity of MurciaMurciaSpain
  3. 3.Biomedical Research Institute of Murcia, University Hospital “Virgen de la Arrixaca”, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasUniversity of MurciaMurciaSpain

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