Multiomic Analyses of Dopaminergic Neurons Isolated from Human Substantia Nigra in Parkinson’s Disease: A Descriptive and Exploratory Study

• Published in: Cellular and molecular neurobiology Vol. 42; no. 8; pp. 2805 - 2818
• Main Authors: Zaccaria, Affif, Antinori, Paola, Licker, Virginie, Kövari, Enikö, Lobrinus, Johannes A., Burkhard, Pierre R.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2022; Springer Nature B.V
• Subjects: Aldehyde dehydrogenase; Autopsy; Biomedical and Life Sciences; Biomedicine; C protein; Cell Biology; CXCR4 protein; Cystatin C; Dopamine receptors; Genes; LRP2 protein; Mass spectroscopy; Movement disorders; Neurobiology; Neurodegenerative diseases; Neurons; Neurosciences; Original Research; Parkinson's disease; Protein expression; Proteins; Proteomics; Ribonucleic acid; RNA; Substantia nigra; Transcriptomics; Dopaminergic neurons; Laser capture microdissection; Transcriptomics; Parkinson’s disease; Proteomics; Human brain tissue
• ISSN: 0272-4340; 1573-6830; 1573-6830
• DOI: 10.1007/s10571-021-01146-8

Dopaminergic neurons (DA) of the substantia nigra pars compacta (SN pc ) selectively and progressively degenerate in Parkinson’s disease (PD). Until now, molecular analyses of DA in PD have been limited to genomic or transcriptomic approaches, whereas, to the best of our knowledge, no proteomic or combined multiomic study examining the protein profile of these neurons is currently available. In this exploratory study, we used laser capture microdissection to extract regions from DA in 10 human SN pc obtained at autopsy in PD patients and control subjects. Extracted RNA and proteins were identified by RNA sequencing and nanoliquid chromatography–mass spectrometry, respectively, and the differential expression between PD and control group was assessed. Qualitative analyses confirmed that the microdissection protocol preserves the integrity of our samples and offers access to specific molecular pathways. This multiomic analysis highlighted differential expression of 52 genes and 33 proteins, including molecules of interest already known to be dysregulated in PD, such as LRP2 , PNMT , CXCR4 , MAOA and CBLN1 genes, or the Aldehyde dehydrogenase 1 protein. On the other hand, despite the same samples were used for both analyses, correlation between RNA and protein expression was low, as exemplified by the CST3 gene encoding for the cystatin C protein. This is the first exploratory study analyzing both gene and protein expression of laser-dissected neuronal parts from SN pc in PD. Data are available via ProteomeXchange with identifier PXD024748 and via GEO with identifier GSE 169755.