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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

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Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons Creative Commons