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The medial and lateral substantia nigra in Parkinson’s disease: mRNA profiles associated with higher brain tissue vulnerability

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Abstract

Sporadic Parkinson’s disease (PD) is characterized by progressive death of dopaminergic neurons within the substantia nigra. However, pathological cell death within this nucleus is not uniform. In PD, the lateral tier of the substantia nigra (SNl) degenerates earlier and more severely than the more medial nigral component (SNm). The cause of this brain regional vulnerability remains unknown. We have used DNA oligonucleotide microarrays to compare gene expression profiles from the SNl to those of the SNm in both PD and control cases. Genes expressed more highly in the PD SNl included the cell death gene, p53 effector related to PMP22, the tumour necrosis factor (TNF) receptor gene, TNF receptor superfamily, member 21, and the mitochondrial complex I gene, NADH dehydrogenase (ubiquinone) 1β subcomplex, 3, 12 kDa (NDUFβ3). Genes that were more highly expressed in PD SNm included the dopamine cell signalling gene, cyclic adenosine monophosphate-regulated phosphoprotein, 21 kDa, the activated macrophage gene, stabilin 1, and two glutathione peroxidase (GPX) genes, GPX1 and GPX3. Thus, there is increased expression of genes encoding pro-inflammatory cytokines and subunits of the mitochondrial electron transport chain, and there is a decreased expression of several glutathione-related genes in the SNl suggesting a molecular basis for pathoclisis. Importantly, some of the genes that are differentially regulated in the SNl are known to be expressed highly or predominately in glial cells. These findings support the view that glial cells can be primarily affected in PD emphasizing the importance of using a whole tissue approach when investigating degenerative CNS disease.

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Acknowledgement

This work was funded by the UK Parkinson’s Disease Society. The Parkinson’s Disease Society Tissue Bank at Imperial College London is a registered charity 948776. We express our deepest appreciation to the donors and their families for donating human brain tissue for research.

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  1. University Department of Neuropathology, Faculty of Medicine, Division of Neuroscience and Mental Health, Imperial College London and Hammersmith Hospitals Trust, Charing Cross campus, Fulham Palace Road, London, W6 8RF, UK

    D. C. Duke, L. B. Moran, R. K. B. Pearce & M. B. Graeber

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  1. D. C. Duke
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  2. L. B. Moran
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  3. R. K. B. Pearce
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Correspondence to M. B. Graeber.

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Duke, D.C., Moran, L.B., Pearce, R.K.B. et al. The medial and lateral substantia nigra in Parkinson’s disease: mRNA profiles associated with higher brain tissue vulnerability. Neurogenetics 8, 83–94 (2007). https://doi.org/10.1007/s10048-006-0077-6

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  • DOI: https://doi.org/10.1007/s10048-006-0077-6

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