Metabolomics is the large-scale study of small molecules, commonly known as metabolites, within cells, biofluids, tissues, or organisms. Collectively, these small molecules and their interactions within a biological system are known as the metabolome. Metabolomics is an emerging technology that holds promise to inform the practice of precision medicine. Now, researchers at the University of California (UC), Davis, report they have created the first atlas of metabolites in the mouse brain. The dataset includes 1,547 different molecules across 10 brain regions in male and female laboratory mice from adolescence through adulthood and into advanced old age.

Their findings are published in the journal Nature Communications in a paper titled, “A metabolome atlas of the aging mouse brain.”

“The mammalian brain relies on neurochemistry to fulfill its functions,” the researchers wrote. “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.”

“This is the largest metabolome analysis available on the brain, worldwide. It covers 1,547 identified metabolites, enabling analysis of many chemical conversions for energy, neurotransmitters, or complex lipids in the brain,” explained Oliver Fiehn, PhD, director of the West Coast Metabolomics Center at the UC Davis Genome Center and senior author.

These findings demonstrate that the brain metabolome is distinct between large brain regions. The team also observed specific sections showed high concentrations of metabolites associated with particular receptors.

In addition, the researchers noted differences in age. “At very old age, energy functions appear to be less efficient, and the myelin sheaths that surround the axons, or wiring, of the brain change composition,” Fiehn said.

Lipid molecules especially showed large differences in aging and across brain regions. These lipids deserve specific investigation to see how they relate to changes in brain function, for example in signaling.

At very old age, the response system against oxidative stress becomes very active, while proteins start breaking down into peptides at an increased rate, he said. These changes are reflected in the metabolome.

“This landmark paper clearly demonstrates the power of the laboratory mouse as a model to accelerate our understanding of brain metabolism, including and especially in humans,” said K.C. Kent Lloyd, PhD, professor and director, UC Davis.

“We show that metabolic changes can be mapped to existing gene and protein brain atlases. The brain metabolome atlas is publicly available and serves as a foundation dataset for future metabolomic studies,” concluded the researchers.

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