Research Paper Volume 12, Issue 19 pp 18889—18906
Increased expression of myelin-associated genes in frontal cortex of SNCA overexpressing rats and Parkinson’s disease patients
- 1 Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen 72076, Germany
- 2 German Center for Neurodegenerative Diseases, Göttingen 37073, Germany
- 3 Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen 37073, Germany
- 4 Department of (Neuro) Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Amsterdam 1105 AZ, The Netherlands
- 5 Max Planck Institute for Experimental Medicine, Göttingen 37073, Germany
- 6 Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle Upon Tyne NE2 4HH, UK
- 7 DFG NGS Competence Center Tübingen, Tübingen 72076, Germany
Received: May 21, 2020 Accepted: August 1, 2020 Published: October 5, 2020https://doi.org/10.18632/aging.103935
How to Cite
Copyright: © 2020 Hentrich et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Parkinson’s disease (PD) is an age-dependent neurodegenerative disorder. Besides characteristic motor symptoms, patients suffer from cognitive impairments linked to pathology in cortical areas. Due to obvious challenges in tracing the underlying molecular perturbations in human brain over time, we took advantage of a well-characterized PD rat model. Using RNA sequencing, we profiled the frontocortical transcriptome of post-mortem patient samples and aligned expression changes with perturbation patterns obtained in the model at 5 and 12 months of age reflecting a presymptomatic and symptomatic time point. Integrating cell type-specific reference data, we identified a shared expression signature between both species that pointed to oligodendrocyte-specific, myelin-associated genes. Drawing on longitudinal information from the model, their nearly identical upregulation in both species could be traced to two distinctive perturbance modes. While one mode exhibited age-independent alterations that affected genes including proteolipid protein 1 (PLP1), the other mode, impacting on genes like myelin-associated glycoprotein (MAG), was characterized by interferences of disease gene and adequate expression adaptations along aging. Our results highlight that even for a group of functionally linked genes distinct interference mechanisms may underlie disease progression that cannot be distinguished by examining the terminal point alone but instead require longitudinal interrogation of the system.