Regional brain iron and gene expression provide insights into neurodegeneration in Parkinson's disease.
Brain
; 144(6): 1787-1798, 2021 07 28.
Article
em En
| MEDLINE
| ID: mdl-33704443
ABSTRACT
The mechanisms responsible for the selective vulnerability of specific neuronal populations in Parkinson's disease are poorly understood. Oxidative stress secondary to brain iron accumulation is one postulated mechanism. We measured iron deposition in 180 cortical regions of 96 patients with Parkinson's disease and 35 control subjects using quantitative susceptibility mapping. We estimated the expression of 15â745 genes in the same regions using transcriptomic data from the Allen Human Brain Atlas. Using partial least squares regression, we then identified the profile of gene transcription in the healthy brain that underlies increased cortical iron in patients with Parkinson's disease relative to controls. Applying gene ontological tools, we investigated the biological processes and cell types associated with this transcriptomic profile and identified the sets of genes with spatial expression profiles in control brains that correlated significantly with the spatial pattern of cortical iron deposition in Parkinson's disease. Gene ontological analyses revealed that these genes were enriched for biological processes relating to heavy metal detoxification, synaptic function and nervous system development and were predominantly expressed in astrocytes and glutamatergic neurons. Furthermore, we demonstrated that the genes differentially expressed in Parkinson's disease are associated with the pattern of cortical expression identified in this study. Our findings provide mechanistic insights into regional selective vulnerabilities in Parkinson's disease, particularly the processes involving iron accumulation.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Encéfalo
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Ferro
Tipo de estudo:
Prognostic_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Brain
Ano de publicação:
2021
Tipo de documento:
Article