Metabolomics of mammalian brain reveals regional differences

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.Electronic supplementary materialThe online version of this article (10.1186/s12918-018-0644-0) contains supplementary material, which is available to authorized users.

Imaging Mass Spectrometry: A New Tool to Assess Molecular Underpinnings of Neurodegeneration

“…Through the investigation of seven neural regions, partitioned into the categories of most damaged, moderately damaged, and lightly damaged by AD pathology, the levels of 55 total metabolites were confirmed to be altered in at least one of those regions [71]. The wide range of regions in which these metabolic abnormalities were seen supports the theory of whole-brain degeneration in AD [71], which could also be contributed to by the regional differences in metabolism, as reported in the mouse brain [14].…”

“…After all, all cells depend on energy metabolism to survive. Without accounting for the regional specificity of metabolites [14], their identification and quantification in a given sample has failed to detect spatially distinct metabolic alterations that may have been important for understanding the disease pathology. The recognition of these shortcomings has increasingly led to harnessing the imaging and profiling capabilities of IMS in the field of neuroscience, in order to better understand and profile the metabolic changes in neurodegenerative diseases, as well as to find potential biomarkers for their diagnosis and monitoring [15].…”

The Status of Bile Acids and Farnesoid X Receptor in Brain and Liver of Rats with Thioacetamide-Induced Acute Liver Failure

“…In most simple terms, the result may manifest a delay in the onset of protein loss vs. the precedent loss of mRNA. The loss of Fxr mRNA may have occurred due to one or a combination of the following events: inhibition of transcription; RNA methylation [ 41 ]; impaired RNA stability, possibly reflecting regional differences in the redox status [ 42 ]. Since the clinical manifestation of ALF is obviously a dynamic process, the documentation of the changes in FXR expression in the brain in the time course of HE progression would be a determining factor.…”

Localization and Functional Characterization of the Alternative Oxidase inNaegleria

“…sodium, potassium, calcium), metals (e.g. iron, copper and magnesium) (Gardner et al ., 2017), metabolites (histidine-containing dipeptides such as anserine, carnosine, b-alanine), cholesterol, poly-unsaturated fatty acids and prostaglandins (Choi et al ., 2018), as well as featuring variable concentrations of oxygen (Özugur, Kunz and Straka, 2020). Differences in the concentrations of these factors have been previously shown to provide stimuli for alterations in the expression of AOX in plants (Vanlerberghe, 2013) and trypanosomes (Vassella et al ., 2004).…”