An Anatomically Resolved Mouse Brain Proteome Reveals Parkinson Disease-relevant Pathways.
Here, we present a mouse brain protein atlas that covers 17 surgically distinct neuroanatomical regions of the adult mouse brain, each less than 1 mm3in 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/.
From the ‡Verna & Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77003; syjung@bcm.edu jqin@bcm.edu.|§Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77003.
Sung Yun
0000-0003-1521-7977
SY
Jung
From the ‡Verna & Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77003.|§Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77003.
Jong Min
JM
Choi
**Department of Molecular and Human Genetics, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas 77003.
Maxime W C
MW
Rousseaux
From the ‡Verna & Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77003.|§Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77003.
Anna
A
Malovannaya
‡‡Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, Texas 77030.
Jean J
JJ
Kim
§§Biosystems Data Analysis, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
Joachim
J
Kutzera
From the ‡Verna & Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77003.|§Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77003.
Yi
Y
Wang
¶¶State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing, China.
Yin
Y
Huang
¶¶State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing, China.
Weimin
W
Zhu
‖‖Advanced Technology Core. Baylor College of Medicine, Houston, Texas 77030; and.
Suman
S
Maity
**Department of Molecular and Human Genetics, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas 77003.|Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030.
Huda Yahya
HY
Zoghbi
From the ‡Verna & Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77003; syjung@bcm.edu jqin@bcm.edu.|§Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77003.|¶¶State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing, China.
Jun
J
Qin
D000818:Animals; D001931:Brain Mapping; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D010300:Parkinson Disease / Q000378:metabolism*; D065842:Pars Compacta / Q000378:metabolism*; D020543:Proteome / Q000032:analysis; D040901:Proteomics / Q000379:methods*; D017557:Ventral Tegmental Area / Q000378:metabolism*
D020543:Proteome