Article (Scientific journals)
The Mouse Brain Metabolome: Region-Specific Signatures and Response to Excitotoxic Neuronal Injury
Jäger, Christian; Glaab, Enrico; Michelucci, Alessandro et al.
2015In American Journal of Pathology, 185 (6), p. 1699-1712
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The original publication is available at http://ajp.amjpathol.org/article/S0002-9440(15)00150-9/abstract


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Keywords :
mouse; brain; metabolomics; bioinformatics; biomarker; neurodegeneration; statistical; machine learning; disease
Abstract :
[en] Neurodegeneration is a multistep process characterized by a multitude of molecular entities and their interactions. Systems' analyses, or omics approaches, have become an important tool in characterizing this process. Although RNA and protein profiling made their entry into this field a couple of decades ago, metabolite profiling is a more recent addition. The metabolome represents a large part or all metabolites in a tissue, and gives a snapshot of its physiology. By using gas chromatography coupled to mass spectrometry, we analyzed the metabolic profile of brain regions of the mouse, and found that each region is characterized by its own metabolic signature. We then analyzed the metabolic profile of the mouse brain after excitotoxic injury, a mechanism of neurodegeneration implicated in numerous neurological diseases. More important, we validated our findings by measuring, histologically and molecularly, actual neurodegeneration and glial response. We found that a specific global metabolic signature, best revealed by machine learning algorithms, rather than individual metabolites, was the most robust correlate of neuronal injury and the accompanying gliosis, and this signature could serve as a global biomarker for neurodegeneration. We also observed that brain lesioning induced several metabolites with neuroprotective properties. Our results deepen the understanding of metabolic changes accompanying neurodegeneration in disease models, and could help rapidly evaluate these changes in preclinical drug studies.
Research center :
Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group)
- Luxembourg Centre for Systems Biomedicine (LCSB): Biomedical Data Science (Glaab Group)
- Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
Luxembourg Centre for Systems Biomedicine (LCSB): Metabolomics (Hiller Group)
Disciplines :
Biotechnology
Neurology
Author, co-author :
Jäger, Christian   ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Glaab, Enrico   ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Michelucci, Alessandro  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Binz, Tina
Köglsberger, Sandra ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Garcia, Pierre  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Trezzi, Jean-Pierre ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Ghelfi, Jenny ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Balling, Rudi ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Buttini, Manuel ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
 These authors have contributed equally to this work.
External co-authors :
yes
Language :
English
Title :
The Mouse Brain Metabolome: Region-Specific Signatures and Response to Excitotoxic Neuronal Injury
Publication date :
2015
Journal title :
American Journal of Pathology
ISSN :
1525-2191
Publisher :
American Society for Investigative Pathology, Bethesda, United States - Maryland
Volume :
185
Issue :
6
Pages :
1699-1712
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 07 May 2015

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