Parkinson mice show functional and molecular changes in the gut long before motoric disease onset

  1. Gries, Manuela
  2. Christmann, Anne
  3. Schulte, Steven
  4. Weyland, Maximilian
  5. Rommel, Stephanie
  6. Martin, Monika
  7. Baller, Marko
  8. Röth, Ralph
  9. Schmitteckert, Stefanie
  10. Unger, Marcus
  11. Liu, Yang
  12. Sommer, Frederik
  13. Mühlhaus, Timo
  14. Schroda, Michael
  15. Timmermans, Jean-Pierre
  16. Pintelon, Isabel
  17. Rappold, Gudrun A.
  18. Britschgi, Markus
  19. Lashuel, Hilal
  20. Menger, Michael D.
  21. Laschke, Matthias W.
  22. Niesler, Beate
  23. Schäfer, Karl-Herbert ORCID logo

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1000 Titel
  • Parkinson mice show functional and molecular changes in the gut long before motoric disease onset
1000 Autor/in
  1. Gries, Manuela |
  2. Christmann, Anne |
  3. Schulte, Steven |
  4. Weyland, Maximilian |
  5. Rommel, Stephanie |
  6. Martin, Monika |
  7. Baller, Marko |
  8. Röth, Ralph |
  9. Schmitteckert, Stefanie |
  10. Unger, Marcus |
  11. Liu, Yang |
  12. Sommer, Frederik |
  13. Mühlhaus, Timo |
  14. Schroda, Michael |
  15. Timmermans, Jean-Pierre |
  16. Pintelon, Isabel |
  17. Rappold, Gudrun A. |
  18. Britschgi, Markus |
  19. Lashuel, Hilal |
  20. Menger, Michael D. |
  21. Laschke, Matthias W. |
  22. Niesler, Beate |
  23. Schäfer, Karl-Herbert |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-06-02
1000 Erschienen in
1000 Quellenangabe
  • 16(1):34
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1186/s13024-021-00439-2 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170976/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Background!#!There is increasing evidence that Parkinson's disease (PD) might start in the gut, thus involving and compromising also the enteric nervous system (ENS). At the clinical onset of the disease the majority of dopaminergic neurons in the midbrain is already destroyed, so that the lack of early biomarkers for the disease represents a major challenge for developing timely treatment interventions. Here, we use a transgenic A30P-α-synuclein-overexpressing PD mouse model to identify appropriate candidate markers in the gut before hallmark symptoms begin to manifest.!##!Methods!#!Based on a gait analysis and striatal dopamine levels, we defined 2-month-old A30P mice as pre-symptomatic (psA30P), since they are not showing any motoric impairments of the skeletal neuromuscular system and no reduced dopamine levels, but an intestinal α-synuclein pathology. Mice at this particular age were further used to analyze functional and molecular alterations in both, the gastrointestinal tract and the ENS, to identify early pathological changes. We examined the gastrointestinal motility, the molecular composition of the ENS, as well as the expression of regulating miRNAs. Moreover, we applied A30P-α-synuclein challenges in vitro to simulate PD in the ENS.!##!Results!#!A retarded gut motility and early molecular dysregulations were found in the myenteric plexus of psA30P mice. We found that i.e. neurofilament light chain, vesicle-associated membrane protein 2 and calbindin 2, together with the miRNAs that regulate them, are significantly altered in the psA30P, thus representing potential biomarkers for early PD. Many of the dysregulated miRNAs found in the psA30P mice are reported to be changed in PD patients as well, either in blood, cerebrospinal fluid or brain tissue. Interestingly, the in vitro approaches delivered similar changes in the ENS cultures as seen in the transgenic animals, thus confirming the data from the mouse model.!##!Conclusions!#!These findings provide an interesting and novel approach for the identification of appropriate biomarkers in men.
1000 Sacherschließung
lokal Protein-and miRNA biomarkers
lokal Mice, Inbred C57BL [MeSH]
lokal Parkinsonian Disorders/physiopathology [MeSH]
lokal Enteric Nervous System/physiopathology [MeSH]
lokal Gastrointestinal Motility/physiology [MeSH]
lokal Animals [MeSH]
lokal Prodromal Symptoms [MeSH]
lokal Gastrointestinal Diseases/etiology [MeSH]
lokal Mice [MeSH]
lokal Gastrointestinal Diseases/physiopathology [MeSH]
lokal Gastrointestinal motility
lokal Early onset
lokal Research Article
lokal Enteric nervous system
lokal Parkinson’s disease
1000 Liste der Beteiligten
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