A metabolome atlas of the aging mouse brain

被引:128
作者
Ding, Jun [1 ,2 ]
Ji, Jian [3 ]
Rabow, Zachary [1 ]
Shen, Tong [1 ]
Folz, Jacob [1 ]
Brydges, Christopher R. [1 ]
Fan, Sili [1 ]
Lu, Xinchen [1 ]
Mehta, Sajjan [1 ]
Showalter, Megan R. [1 ]
Zhang, Ying [1 ]
Araiza, Renee [4 ,5 ]
Bower, Lynette R. [4 ,5 ]
Lloyd, K. C. Kent [4 ,5 ]
Fiehn, Oliver [1 ]
机构
[1] Univ Calif Davis, West Coast Metabol Ctr, UC Davis Genome Ctr, 451 Hlth Sci Dr, Davis, CA 95616 USA
[2] Wuhan Univ, Dept Chem, Wuhan 430072, Hubei, Peoples R China
[3] Jiangnan Univ, Natl Engn Res Ctr Funct Foods, Synerget Innovat Ctr Food Safety & Nutr, Sch Food Sci,State Key Lab Food Sci & Technol, Wuxi 214122, Jiangsu, Peoples R China
[4] Univ Calif Davis, Sch Med, Mouse Biol Program, Davis, CA 95618 USA
[5] Univ Calif Davis, Sch Med, Dept Surg, Davis, CA 95618 USA
基金
中国博士后科学基金;
关键词
GENE-EXPRESSION; MASS-SPECTROMETRY; RESTING-STATE; OLIGODENDROCYTE; MYELIN; CONNECTIVITY; DYNAMICS; CELLS;
D O I
10.1038/s41467-021-26310-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The mammalian brain relies on neurochemistry to fulfill its functions. Yet, the complexity of the brain metabolome and its changes during diseases or aging remain poorly understood. Here, we generate a metabolome atlas of the aging wildtype mouse brain from 10 anatomical regions spanning from adolescence to old age. We combine data from three assays and structurally annotate 1,547 metabolites. Almost all metabolites significantly differ between brain regions or age groups, but not by sex. A shift in sphingolipid patterns during aging related to myelin remodeling is accompanied by large changes in other metabolic pathways. Functionally related brain regions (brain stem, cerebrum and cerebellum) are also metabolically similar. In cerebrum, metabolic correlations markedly weaken between adolescence and adulthood, whereas at old age, cross-region correlation patterns reflect decreased brain segregation. We show that metabolic changes can be mapped to existing gene and protein brain atlases. The brain metabolome atlas is publicly available (https://mouse.atlas.metabolomics.us/) and serves as a foundation dataset for future metabolomic studies.
引用
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页数:12
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共 66 条
  • [1] A comprehensive transcriptional map of primate brain development
    Bakken, Trygve E.
    Miller, Jeremy A.
    Ding, Song-Lin
    Sunkin, Susan M.
    Smith, Kimberly A.
    Ng, Lydia
    Szafer, Aaron
    Dalley, Rachel A.
    Royall, Joshua J.
    Lemon, Tracy
    Shapouri, Sheila
    Aiona, Kaylynn
    Arnold, James
    Bennett, Jeffrey L.
    Bertagnolli, Darren
    Bickley, Kristopher
    Boe, Andrew
    Brouner, Krissy
    Butler, Stephanie
    Byrnes, Emi
    Caldejon, Shiella
    Carey, Anita
    Cate, Shelby
    Chapin, Mike
    Chen, Jefferey
    Dee, Nick
    Desta, Tsega
    Dolbeare, Tim A.
    Dotson, Nadia
    Ebbert, Amanda
    Fulfs, Erich
    Gee, Garrett
    Gilbert, Terri L.
    Goldy, Jeff
    Gourley, Lindsey
    Gregor, Ben
    Gu, Guangyu
    Hall, Jon
    Haradon, Zeb
    Haynor, David R.
    Hejazinia, Nika
    Hoerder-Suabedissen, Anna
    Howard, Robert
    Jochim, Jay
    Kinnunen, Marty
    Kriedberg, Ali
    Kuan, Chihchau L.
    Lau, Christopher
    Lee, Chang-Kyu
    Lee, Felix
    [J]. NATURE, 2016, 535 (7612) : 367 - +
  • [2] Modular Segregation of Structural Brain Networks Supports the Development of Executive Function in Youth
    Baum, Graham L.
    Ciric, Rastko
    Roalf, David R.
    Betzel, Richard F.
    Moore, Tyler M.
    Shinohara, Russell T.
    Kahn, Ari E.
    Vandekar, Simon N.
    Rupert, Petra E.
    Quarmley, Megan
    Cook, Philip A.
    Elliott, Mark A.
    Ruparel, Kosha
    Gur, Raquel E.
    Gur, Ruben C.
    Bassett, Danielle S.
    Satterthwaite, Theodore D.
    [J]. CURRENT BIOLOGY, 2017, 27 (11) : 1561 - +
  • [3] Biology of oligodendrocyte and myelin in the mammalian central nervous system
    Baumann, N
    Pham-Dinh, D
    [J]. PHYSIOLOGICAL REVIEWS, 2001, 81 (02) : 871 - 927
  • [4] Differential expression of (dihydro)ceramide synthases in mouse brain: oligodendrocyte-specific expression of CerS2/Lass2
    Becker, Ivonne
    Wang-Eckhardt, Lihua
    Yaghootfam, Afshin
    Gieselmann, Volkmar
    Eckhardt, Matthias
    [J]. HISTOCHEMISTRY AND CELL BIOLOGY, 2008, 129 (02) : 233 - 241
  • [5] The social brain in adolescence
    Blakemore, Sarah-Jayne
    [J]. NATURE REVIEWS NEUROSCIENCE, 2008, 9 (04) : 267 - 277
  • [6] Software Tools and Approaches for Compound Identification of LC-MS/MS Data in Metabolomics
    Blazenovic, Ivana
    Kind, Tobias
    Ji, Jian
    Fiehn, Oliver
    [J]. METABOLITES, 2018, 8 (02):
  • [7] The origin of correlations in metabolomics data
    Camacho, Diogo
    de la Fuente, Alberto
    Mendes, Pedro
    [J]. METABOLOMICS, 2005, 1 (01) : 53 - 63
  • [8] Altering sphingolipid composition with aging induces contractile dysfunction of gastric smooth muscle via KCa1.1 upregulation
    Choi, Shinkyu
    Kim, Ji Aee
    Kim, Tae Hun
    Li, Hai-yan
    Shin, Kyong-Oh
    Lee, Yong-Moon
    Oh, Seikwan
    Pewzner-Jung, Yael
    Futerman, Anthony H.
    Suh, Suk Hyo
    [J]. AGING CELL, 2015, 14 (06) : 982 - 994
  • [9] Metabolomics of mammalian brain reveals regional differences
    Choi, William T.
    Tosun, Mehmet
    Jeong, Hyun-Hwan
    Karakas, Cemal
    Semerci, Fatih
    Liu, Zhandong
    Maletic-Savatic, Mirjana
    [J]. BMC SYSTEMS BIOLOGY, 2018, 12
  • [10] A brainwide atlas of synapses across the mouse life span
    Cizeron, Melissa
    Qiu, Zhen
    Koniaris, Babis
    Gokhale, Ragini
    Komiyama, Noboru H.
    Fransen, Erik
    Grant, Seth G. N.
    [J]. SCIENCE, 2020, 369 (6501) : 270 - +