Evidence for Gender-Specific Transcriptional Profiles of Nigral Dopamine Neurons in Parkinson Disease

BACKGROUND: Epidemiological data suggest that the male gender is one of the risks factors for the development of Parkinson Disease (PD). Also, differences in the clinical manifestation and the course of PD have been observed between males and females. However, little is known about the molecular aspects underlying gender-specificity in PD. To address this issue, we determined the gene expression profiles of male and female dopamine (DA) neurons in sporadic PD. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed Affymetrix-based microarrays on laser microdissected DA neurons from postmortem brains of sporadic PD patients and age-matched controls across genders. Pathway enrichment demonstrated that major cellular pathways involved in PD pathogenesis showed different patterns of deregulation between males and females with more prominent downregulation of genes related to oxidative phosporylation, apoptosis, synaptic transmission and transmission of nerve impulse in the male population. In addition, we found upregulation of gene products for metabolic processes and mitochondrial energy consumption in the age-matched male control neurons. On the single cell level, selected data validation using quantitative Real-Time (qRT)-PCR was consistent with microarray raw data and supported some of the observations from data analysis. CONCLUSIONS/SIGNIFICANCE: On the molecular level, our results provide evidence that the expression profiles of aged normal and PD midbrain DA neurons are gender-specific. The observed differences in the expression profiles suggest a disease bias of the male gender, which could be in concordance with clinical observations that the male gender represents a risk factor for sporadic PD. Validation of gene expression by qRT-PCR supported the microarray results, but also pointed to several caveats involved in data interpretation.