TY - JOUR
T1 - Increased expression of myelin-associated genes in frontal cortex of SNCA overexpressing rats and Parkinson's disease patients
AU - Hentrich, Thomas
AU - Wassouf, Zinah
AU - Ehrhardt, Christine
AU - Haas, Eva
AU - Mills, James D.
AU - Aronica, Eleonora
AU - Outeiro, Tiago Fleming
AU - Hübener-Schmid, Jeannette
AU - Riess, Olaf
AU - Casadei, Nicolas
AU - Schulze-Hentrich, Julia M.
PY - 2020/10/15
Y1 - 2020/10/15
N2 - 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.
AB - 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.
KW - Parkinson's disease
KW - frontal cortex
KW - myelination
KW - oligodendrocytes
KW - transcriptome analysis
UR - http://www.scopus.com/inward/record.url?scp=85093924966&partnerID=8YFLogxK
U2 - https://doi.org/10.18632/aging.103935
DO - https://doi.org/10.18632/aging.103935
M3 - Article
C2 - 33017301
SN - 1945-4589
VL - 12
SP - 18889
EP - 18906
JO - Aging
JF - Aging
IS - 19
ER -