Energy Profiles of Neurons and Glial Cells in the Human Brain
Poster No:
888
Submission Type:
Abstract Submission
Authors:
Laura Fraticelli1, Gabriel Castrillón2, Valentin Riedl3
Institutions:
1Klinikum rechts der Isar der Technischen Universität München, Munich, Bavaria, 2Friedrich-Alexander University, Erlangen, Germany, 3Technical University of Munich, Erlangen, Germany
First Author:
Co-Author(s):
Introduction:
Brain cells exhibit divergent metabolic profiles that have been mainly studied in animal models and in-vitro. Neurons are recognized as oxidative cells, and astrocytes (Ast) are glycolytic. Lipid and fatty acid (FA) oxidation occurs primarily in glial cells (Ast, microglia (Mic) and oligodendrocytes (OLs)) and is pivotal for normal brain function. Furthermore, Mic are metabolically versatile as the brain's resident immune cells and OLs are essential for the myelination of axons. These preferential cell profiles have not been validated in the human brain. Metabolic differences within the cell types emerge predominantly from differential gene expressions. Transcriptomic data of post-mortem brains from the Allen Human Brain Atlas (AHBA) enabled us to investigate the expression patterns of metabolism and cell type-related genes in cortical and subcortical areas of the human brain.
Methods:
The spatial microarray data from the AHBA was processed through abagen to study the energy profiles of neurons and glial cells. Left hemisphere data was assigned to the HCPex parcellation, an extended version of the HCP-MMP1, including subcortical areas. Microarray data was normalized and aggregated across donors' brains to generate expression maps of 15637 genes across 203 regions. Cell types and metabolic pathways were represented by the expression of distinct gene sets. Pathways of interest were glycolysis (Gly), oxidative phosphorylation (OxPhos), FA metabolism, reactive oxygen species (ROS), peroxisome (Per) and myelin-related (My) genes. Cell-type markers were extracted from Seidlitz et al. 2020. The median expression of cell-type and metabolic gene sets was plotted according to the 203 HCPex areas. Spearman correlation was calculated between cell-type and metabolic expression maps and tested for significance through t-tests. P-values were Bonferroni adjusted.
Results:
The median of cell-type and metabolic expression maps revealed alternating expression patterns in cortical and subcortical areas. In subcortical areas, the expression of excitatory and inhibitory neurons (ExNeu and InhNeu) decreased substantially, while Ast, OL and Mic increased. Similar to the glial expression maps, Fa, Per and My increased subcortically. Gly and OxPhos genes are stably expressed across cortex and subcortex.
We found divergent correlation patterns in cortical versus subcortical areas. In cortical areas, ExNeu correlated positively with Gly, OxPhos, and ROS. Both ExNeu and InhNeu correlated negatively with My. Ast correlated positively with Gly, FA, Per and My. Mic showed positive correlations with Gly, ROS, FA, Per and My, while OLs correlated with Per and My. In subcortical areas merely Mic and OLs showed significant correlations with metabolic gene sets. Mic correlated positively with Ox, ROS, FA, My and OLs with Gly, Ox, FA, Per, and My.
We found divergent correlation patterns in cortical versus subcortical areas. In cortical areas, ExNeu correlated positively with Gly, OxPhos, and ROS. Both ExNeu and InhNeu correlated negatively with My. Ast correlated positively with Gly, FA, Per and My. Mic showed positive correlations with Gly, ROS, FA, Per and My, while OLs correlated with Per and My. In subcortical areas merely Mic and OLs showed significant correlations with metabolic gene sets. Mic correlated positively with Ox, ROS, FA, My and OLs with Gly, Ox, FA, Per, and My.
Conclusions:
Studies on the human brain focus predominantly on the cerebral cortex, even though the subcortex is pivotal for cognitive functions. The HCPex enabled us to follow expression patterns of cell- and metabolism-specific genes across cortical and subcortical areas. Glia to neuron ratio is higher in subcortical regions, which is reflected in decreased neuronal and increased glial marker expression in subcortical areas. Glia-related metabolic pathways increased concordantly. Our correlation analysis underpinned that excitatory neurotransmission consumes majority of the brain's energy. Gly, OxPhos and ROS correlated with ExNeu but not InhNeu. Glial cells are mainly responsible for FA and lipid metabolism, with FA oxidation primarily occurring in astrocytes. Peroxisomes are essential for FA α-oxidation and the biosynthesis of myelin sheath lipids. Accordingly, we find correlations between glial cells, FA, and Per. Intriguingly, neuronal and glial cells display diverging correlation patterns in subcortical areas highlighting distinct cellular and metabolic organization in the human cortex and subcortex.
Genetics:
Transcriptomics 1
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Cortical Anatomy and Brain Mapping
Subcortical Structures
Physiology, Metabolism and Neurotransmission :
Cerebral Metabolism and Hemodynamics 2
Physiology, Metabolism and Neurotransmission Other
Keywords:
Astrocyte
Cellular
Cortex
Glia
Neuron
Structures
Sub-Cortical
1|2Indicates the priority used for review
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