An Anatomically Resolved Mouse Brain Proteome Reveals Parkinson Disease-relevant Pathways

• Published in: Molecular & cellular proteomics Vol. 16; no. 4; pp. 581 - 593
• Main Authors: Jung, Sung Yun, Choi, Jong Min, Rousseaux, Maxime W.C., Malovannaya, Anna, Kim, Jean J., Kutzera, Joachim, Wang, Yi, Huang, Yin, Zhu, Weimin, Maity, Suman, Zoghbi, Huda Yahya, Qin, Jun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2017; American Society for Biochemistry and Molecular Biology; The American Society for Biochemistry and Molecular Biology
• Subjects: Anatomy; Animals; Brain; Brain architecture; Brain Mapping; Disease Models, Animal; Gene expression; Gene Expression Regulation; Genotypes; Humans; Mice; Movement disorders; Neurodegenerative diseases; Neurological diseases; Parkinson Disease - metabolism; Parkinson's disease; Pars Compacta - metabolism; Proteins; Proteome - analysis; Proteomics - methods; Rodents; Substantia nigra; Ventral Tegmental Area - metabolism; Ventral tegmentum
• ISSN: 1535-9476; 1535-9484
• DOI: 10.1074/mcp.M116.061440

Here, we present a mouse brain protein atlas that covers 17 surgically distinct neuroanatomical regions of the adult mouse brain, each less than 1 mm3 in size. The protein expression levels are determined for 6,500 to 7,500 gene protein products from each region and over 12,000 gene protein products for the entire brain, documenting the physiological repertoire of mouse brain proteins in an anatomically resolved and comprehensive manner. We explored the utility of our spatially defined protein profiling methods in a mouse model of Parkinson's disease. We compared the proteome from a vulnerable region (substantia nigra pars compacta) of wild type and parkinsonian mice with that of an adjacent, less vulnerable, region (ventral tegmental area) and identified several proteins that exhibited both spatiotemporal- and genotype-restricted changes. We validated the most robustly altered proteins using an alternative profiling method and found that these modifications may highlight potential new pathways for future studies. This proteomic atlas is a valuable resource that offers a practical framework for investigating the molecular intricacies of normal brain function as well as regional vulnerability in neurological diseases. All of the mouse regional proteome profiling data are published on line at http://mbpa.bprc.ac.cn/.