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doi:10.22028/D291-44097
Titel: | Parkinson mice show functional and molecular changes in the gut long before motoric disease onset |
VerfasserIn: | Gries, Manuela Christmann, Anne Schulte, Steven Weyland, Maximilian Rommel, Stephanie Martin, Monika Baller, Marko Röth, Ralph Schmitteckert, Stefanie Unger, Marcus Liu, Yang Sommer, Frederik Mühlhaus, Timo Schroda, Michael Timmermans, Jean-Pierre Pintelon, Isabel Rappold, Gudrun A. Britschgi, Markus Lashuel, Hilal Menger, Michael D. Laschke, Matthias W. Niesler, Beate Schäfer, Karl-Herbert |
Sprache: | Englisch |
Titel: | Molecular Neurodegeneration |
Bandnummer: | 16 |
Heft: | 1 |
Verlag/Plattform: | BMC |
Erscheinungsjahr: | 2021 |
Freie Schlagwörter: | Parkinson’s disease Early onset Enteric nervous system Gastrointestinal motility Protein-and miRNA biomarkers |
DDC-Sachgruppe: | 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | 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-αsynuclein-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. |
DOI der Erstveröffentlichung: | 10.1186/s13024-021-00439-2 |
URL der Erstveröffentlichung: | https://doi.org/10.1186/s13024-021-00439-2 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-440973 hdl:20.500.11880/39447 http://dx.doi.org/10.22028/D291-44097 |
ISSN: | 1750-1326 |
Datum des Eintrags: | 22-Jan-2025 |
Bezeichnung des in Beziehung stehenden Objekts: | Supplementary Information |
In Beziehung stehendes Objekt: | https://static-content.springer.com/esm/art%3A10.1186%2Fs13024-021-00439-2/MediaObjects/13024_2021_439_MOESM1_ESM.docx https://static-content.springer.com/esm/art%3A10.1186%2Fs13024-021-00439-2/MediaObjects/13024_2021_439_MOESM2_ESM.zip https://static-content.springer.com/esm/art%3A10.1186%2Fs13024-021-00439-2/MediaObjects/13024_2021_439_MOESM3_ESM.zip https://static-content.springer.com/esm/art%3A10.1186%2Fs13024-021-00439-2/MediaObjects/13024_2021_439_MOESM4_ESM.zip https://static-content.springer.com/esm/art%3A10.1186%2Fs13024-021-00439-2/MediaObjects/13024_2021_439_MOESM5_ESM.zip |
Fakultät: | M - Medizinische Fakultät |
Fachrichtung: | M - Neurologie und Psychiatrie |
Professur: | M - Prof. Dr. Klaus Faßbender |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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s13024-021-00439-2.pdf | 7,95 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons