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Increased expression of myelin-associated genes in frontal cortex of SNCA overexpressing rats and Parkinson’s disease patients

ABSTRACT: Parkinson’s disease 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 molecular perturbations underlying alterations in human brain over time, we took advantage of a well-characterized 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 allowed tracing them to two distinctive perturbance modes they originate from. While one mode exhibited age-independent alterations that affected genes like PLP1, the other mode, impacting on genes like MAG, was characterized by interferences of disease gene and adequate adaptations of gene activity along ageing. Our results highlight that even for a small set of functionally linked genes distinct interference mechanisms may underly disease progression that cannot be distinguished by examining the terminal point alone but instead require longitudinal interrogation of the system.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE150646 | GEO | 2020/12/21

REPOSITORIES: GEO

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