Changes in the sympathetic innervation of the gut in rotenone treated mice as possible early biomarker for Parkinson’s disease

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Mike Arnhold - , Department of Neurology (Author)
  • Yanina Dening - , Ludwig Maximilian University of Munich, Munich Cluster for Systems Neurology (SyNergy) (Author)
  • Michaël Chopin - , Walter and Eliza Hall Institute of Medical Research (WEHI), University of Melbourne (Author)
  • Esteban Arévalo - , Institute of Anatomy (Author)
  • Mathias Schwarz - , Institute of Anatomy (Author)
  • Heinz Reichmann - , Department of Neurology, Center for Regenerative Therapies Dresden (Author)
  • Gabriele Gille - , Department of Neurology (Author)
  • Richard H.W. Funk - , Institute of Anatomy, Center for Regenerative Therapies Dresden (CRTD) (Author)
  • Francisco Pan-Montojo - , Ludwig Maximilian University of Munich, Munich Cluster for Systems Neurology (SyNergy) (Author)

Abstract

Introduction: Involvement of the peripheral nervous system (PNS) is relatively common in Parkinson’s disease (PD) patients. PNS alterations appear early in the course of the disease and are responsible for some of the non-motor symptoms observed in PD patients. In previous studies, we have shown that environmental toxins can trigger the disease by acting on the enteric nervous system. Material and methods: Here, we analyzed the effect of mitochondrial Complex I inhibition on sympathetic neuritis in vivo and sympathetic neurons in vitro. Combining in vivo imaging and protein expression profiling. Results: we found that rotenone, a widely used mitochondrial Complex I inhibitor decreases the density of sympathetic neurites innervating the gut in vivo, while in vitro, it induces the redistribution of intracellular alpha-synuclein and neurite degeneration. Interestingly, sympathetic neurons are much more resistant to rotenone exposure than mesencephalic dopaminergic neurons. Conclusion: Altogether, these results suggest that enteric sympathetic denervation could be an initial pre-motor alteration in PD progression that could be used as an early biomarker of the disease.

Details

Original languageEnglish
Pages (from-to)211-222
Number of pages12
JournalClinical autonomic research
Volume26
Issue number3
Publication statusPublished - 1 Jun 2016
Peer-reviewedYes

External IDs

PubMed 27178445

Keywords

Keywords

  • Biomarker, Constipation, alpha-synuclein pathology, Enteric sympathetic innervation, Parkinson’s disease