Marcus Unger, Germany
Saarland University NeurologyAuthor Of 1 Presentation
PARKINSON MICE SHOW FUNCTIONAL AND MOLECULAR CHANGES IN THE GUT LONG BEFORE MOTORIC DISEASE ONSET
Abstract
Aims
There is increasing evidence that Parkinson’s disease (PD) might start in the gut, thus involving and compromising the enteric nervous system (ENS). The lack of early biomarkers for PD represents a major challenge for developing timely treatment interventions. Here, we use a PD mouse model to identify appropriate candidate markers in the gut before hallmark symptoms begin to manifest.
Methods
Based on a gait analysis we defined 2-month-old A30P mice as pre-symptomatic (psA30P), since they are not showing any motoric impairments. 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 gastrointestinal motility, molecular composition of the ENS, and the expression of regulating miRNAs. Moreover, we applied 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 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 to identify appropriate biomarkers in men.