LRRK2 mutations are the most common genetic cause of Parkinsons disease (PD). We performed a whole-genome RNA profiling of locus coeruleus post-mortem tissue from idiopathic PD (IPD) and LRRK2-associated PD patients. The differentially expressed genes found in IPD and LRRK2-associated PD were involved in the gene ontology terms of synaptic transmission and neuron projection. In addition, in the IPD group we found associated genes belonging to the immune system. Pathway analysis of the differentially expressed genes in IPD was related with neuroactive-ligand receptor interaction and with immune system pathways. Specifically, the analysis highlighted differential expression of genes located in the chromosome 6p21.3 belonging to the class II HLA. Our findings support the hypothesis of a potential role of neuroinflammation and the involvement of the HLA genetic area in IPD pathogenesis. Future studies are necessary to shed light on the relation of immune system related pathways in the etiopathogenesis of PD.
Brain transcriptomic profiling in idiopathic and LRRK2-associated Parkinson's disease.
Sex, Specimen part, Disease
View SamplesLRRK2 mutations are the most common genetic cause of Parkinsons disease (PD). We performed a whole-genome RNA profiling of putamen tissue from idiopathic PD (IPD), LRRK2-associated PD (G2019S mutation), neurologically healthy controls and one asymptomatic LRRK2 mutation carrier, by using the Genechip Human Exon 1.0-ST Array. The differentially expressed genes found in IPD revealed an alteration of biological pathways related to long term potentiation (LTP), GABA receptor signalling, and calcium signalling pathways, among others. These pathways are mainly related with cell signalling cascades and synaptic plasticity processes. They were also altered in the asymptomatic LRRK2 mutation carrier but not in the LRRK2-associated PD group. The expression changes seen in IPD might be attributed to an adaptive consequence of a dysfunction in the dopamine transmission. The lack of these altered molecular pathways in LRRK2-associated PD patients suggests that these cases could show a different molecular response to dopamine transmission impairment.
Microarray expression analysis in idiopathic and LRRK2-associated Parkinson's disease.
Sex
View SamplesThe aim of the study was to evaluate cocaine-induced changes in gene expression in a dopaminergic model.
Transcriptomic and genetic studies identify NFAT5 as a candidate gene for cocaine dependence.
Cell line, Treatment
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