Abstract
BackgroundThe mammalian brain is organized into regions with specific biological functions and properties. These regions have distinct transcriptomes, but little is known whether they may also differ in their metabolome. The metabolome, a collection of small molecules or metabolites, is at the intersection of the genetic background of a given cell or tissue and the environmental influences that affect it. Thus, the metabolome directly reflects information about the physiologic state of a biological system under a particular condition. The objective of this study was to investigate whether various brain regions have diverse metabolome profiles, similarly to their genetic diversity. The answer to this question would suggest that not only the genome but also the metabolome may contribute to the functional diversity of brain regions.MethodsWe investigated the metabolome of four regions of the mouse brain that have very distinct functions: frontal cortex, hippocampus, cerebellum, and olfactory bulb. We utilized gas- and liquid- chromatography mass spectrometry platforms and identified 215 metabolites.ResultsPrincipal component analysis, an unsupervised multivariate analysis, clustered each brain region based on its metabolome content, thus providing the unique metabolic profile of each region. A pathway-centric analysis indicated that olfactory bulb and cerebellum had most distinct metabolic profiles, while the cortical parenchyma and hippocampus were more similar in their metabolome content. Among the notable differences were distinct oxidative-anti-oxidative status and region-specific lipid profiles. Finally, a global metabolic connectivity analysis using the weighted correlation network analysis identified five hub metabolites that organized a unique metabolic network architecture within each examined brain region. These data indicate the diversity of global metabolome corresponding to specialized regional brain function and provide a new perspective on the underlying properties of brain regions.ConclusionIn summary, we observed many differences in the metabolome among the various brain regions investigated. All four brain regions in our study had a unique metabolic signature, but the metabolites came from all categories and were not pathway-centric.
Highlights
The mammalian brain is organized into regions with specific biological functions and properties
Untargeted mass spectrometry profiling Metabolon, Inc. used three independent platforms (ultrahigh performance liquid chromatography/tandem mass spectrometry (UHPLC/Mass spectrometry (MS)-MS2) optimized for basic species, UHPLC/MS-MS2 optimized for acidic species, and gas chromatography/mass spectrometry (GC/ MS)) to generate untargeted high-throughput mass spectrometry-identified metabolites in the brain regions
Brain metabolome is enriched in several classes of metabolites Using UHPLC/MS-MS2 optimized for basic species, UHPLC/MS-MS2 optimized for acidic species, and Gas chromatography (GC)/ MS, we performed untargeted high-throughput mass spectrometry and identified metabolites in four mouse brain regions: olfactory bulb, frontal cortex, hippocampus, and cerebellum (N = 6 per region)
Summary
The mammalian brain is organized into regions with specific biological functions and properties These regions have distinct transcriptomes, but little is known whether they may differ in their metabolome. The metabolome directly reflects information about the physiologic state of a biological system under a particular condition. The objective of this study was to investigate whether various brain regions have diverse metabolome profiles, to their genetic diversity. Pathologic conditions mostly disturb normal metabolic processes, resulting in changes that can be observed as metabolic signatures [5,6,7,8,9,10,11,12] Tracing these metabolic signatures could reveal information about the physiologic state of the brain under a particular condition [13]
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