期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 15, 页码 6181-6186出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1019164108
关键词
cognition; glutamate; development
资金
- Ministry of Science and Technology of the People's Republic of China [2007CB947004, 2006CB910700, 2011CB910200]
- Max Planck
- Chinese Academy of Sciences [KSCX2-YW-R-094, KSCX2-YW-R-251]
- Shanghai Institutes for Biological Sciences [2008KIT104]
- European Union
- Max Planck Society
- Bundesministerum fuer Bildung und Forschung
Human evolution is characterized by the rapid expansion of brain size and drastic increase in cognitive capabilities. It has long been suggested that these changes were accompanied by modifications of brain metabolism. Indeed, human-specific changes on gene expression or amino acid sequence were reported for a number of metabolic genes, but actual metabolite measurements in humans and apes have remained scarce. Here, we investigate concentrations of more than 100 metabolites in the prefrontal and cerebellar cortex in 49 humans, 11 chimpanzees, and 45 rhesus macaques of different ages using gas chromatography-mass spectrometry (GC-MS). We show that the brain metabolome undergoes substantial changes, both ontogenetically and evolutionarily: 88% of detected metabolites show significant concentration changes with age, whereas 77% of these metabolic changes differ significantly among species. Although overall metabolic divergence reflects phylogenetic relationships among species, we found a fourfold acceleration of metabolic changes in prefrontal cortex compared with cerebellum in the human lineage. These human-specific metabolic changes are paralleled by changes in expression patterns of the corresponding enzymes, and affect pathways involved in synaptic transmission, memory, and learning.
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