Transcriptomic alterations in fibroblast from parkinson's disease patients at high glucose levels

In this study, we evaluate the hypothesis that molecular pathways in a cell model of Parkinson’s disease (PD) could be altered depending of glucose levels. We cultured fibroblasts from sporadic PD (sPD; n=4), PD patients carrying LRRK2 mutations (LRRK2-PD; n=3) and healthy controls (HC; n=4) at high (25 mM) and low (5 mM) glucose and analysed the transcriptome profile by using whole RNA sequencing. We found 1439 differentially expressed transcripts (DET) comparing HC with overall PD cases. These genes are related with THE gene ontology terms cytosqueleton, cell adhesion, protein translation and ribosomes, mitochondrial electron transport between others, when cultured at 25 mM of glucose. However, at 5 mM there are virtually no gene expression changes in PD compared to controls. When compared between 5 and 25 mM condition separately for each group HC and PD, we found 1482 DET in controls, and 3381 in PD cases, but only found altered significant gene ontology terms in PD. These findings suggest that high glucose levels cause specific molecular changes in fibroblasts which is exacerbated in PD, potentially leading to non adaptive changes. This work emphasizes the importance of energetic balance in PD and the need of further research about the role of glucose levels in clinical studies. Examination of fibroblast expression by RNA seq at low (5 mM) and high (25 mM) glucose levels