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

Lookup NU author(s): Professor Tiago OuteiroORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2020 Hentrich et al.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.

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Author(s): Hentrich T, Wassouf Z, Ehrhardt C, Haas E, Mills JD, Casadei N, Outeiro TF, Hubener-Schmid J, Riess O, Casadei N, Schulze-Hentrich JM

Publication type: Article

Publication status: Published

Journal: Aging

Year: 2020

Volume: 12

Issue: 19

Pages: 18889-18906

Online publication date: 05/10/2020

Acceptance date: 01/08/2020

Date deposited: 10/12/2020

ISSN (electronic): 1945-4589

Publisher: Impact Journals LLC

URL: https://doi.org/10.18632/aging.103935

DOI: 10.18632/aging.103935

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