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Next Generation Sequencing facilitated analysis of gene expression differences in the subthalamic nucleus (STN) between Parkinson's and Normal post-mortem human brains

ABSTRACT: Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder with the characteristic feature of extensive death of dopaminergic neurons in the substantia nigra. The global decrease in dopamine levels within the basal ganglia leads to the emergence of distinctive pathophysiology in multiple signalling midbrain regions. The subthalamic nucleus (STN) is one of the critical basal ganglia nuclei affected, which displays elevated excitatory activation in PD and contributes to the cardinal hypokinetic motor symptoms. In order to better understand the role of the STN in PD, we have investigated the human STN transcriptome in seven PD and nine neurologically normal post-mortem brains. Differential gene expression analysis conducted between PD and normal brains yielded 159 genes with changes in expression, 128 up-regulated and 31 down-regulated, in the PD STN. Collectively, the up-regulated genes showed enrichment in multiple cellular processes including neuroinflammation, immune response, regulation of cell death and blood vessel homeostasis. Conversely, the down-regulated genes showed profound dysregulation of dopamine biosynthetic and metabolic processes. The differential transcription of a subset of genes identified in the transcriptome analysis was then further validated using the Nanostring nCounter system, confirming expression differences in 21 of 26 assessed genes. Furthermore, the transcription factor MafF, which showed the largest fold change from both RNA-seq and nanostring was demonstrated to be induced under pro-inflammatory conditions. Although the STN constitutes one of the brain regions that shows minimal neurodegeneration in PD, our differential gene expression data suggest that this structure is fundamentally altered in PD.

ORGANISM(S): Homo sapiens

PROVIDER: GSE106608 | GEO | 2021/05/01

REPOSITORIES: GEO

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Next Generation Sequencing facilitated analysis of gene expression differences in the subthalamic nucleus (STN) between Parkinson's and Normal post-mortem human brains

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