Glial Cell Metabolic Profile Upon Iron Deficiency: Oligodendroglial and Astroglial Casualties of Bioenergetic Adjustments

Iron deficiency (ID) represents one of the most prevalent nutritional deficits, affecting almost two billion people worldwide. Gestational iron deprivation induces hypomyelination due to oligodendroglial maturation deficiencies and is thus a useful experimental model to analyze oligodendrocyte (OLG)...

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Bibliographic Details
Published in:Molecular neurobiology 2023-04, Vol.60 (4), p.1949-1963
Main Authors: Rosato-Siri, María Victoria, Adami, Pamela V. Martino, Guitart, María Eugenia, Verstraeten, Sandra, Morelli, Laura, Correale, Jorge, Pasquini, Juana María
Format: Article
Language:English
Subjects:
Acidification
Astrocytes
Bioenergetics
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cell fate
Energy Metabolism
Glial cells
Glycogen
Humans
Iron
Iron Deficiencies
Iron deficiency
Metabolism
Metabolome
Mitochondria
Neonates
Neurobiology
Neurology
Neurosciences
Nutrient deficiency
Oligodendroglia - metabolism
Oxygen consumption
Proteomics
Structural proteins
Tricarboxylic acid cycle
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Summary:Iron deficiency (ID) represents one of the most prevalent nutritional deficits, affecting almost two billion people worldwide. Gestational iron deprivation induces hypomyelination due to oligodendroglial maturation deficiencies and is thus a useful experimental model to analyze oligodendrocyte (OLG) requirements to progress to a mature myelinating state. A previous proteomic study in the adult ID brain by our group demonstrated a pattern of dysregulated proteins involved in the tricarboxylic acid cycle and mitochondrial dysfunction. The aim of the present report was to assess bioenergetics metabolism in primary cultures of OLGs and astrocytes (ASTs) from control and ID newborns, on the hypothesis that the regulation of cell metabolism correlates with cell maturation. Oxygen consumption and extracellular acidification rates were measured using a Seahorse extracellular flux analyzer. ID OLGs and ASTs both exhibited decreased spare respiratory capacity, which indicates that ID effectively induces mitochondrial dysfunction. A decrease in glycogen granules was observed in ID ASTs, and an increase in ROS production was detected in ID OLGs. Immunolabeling of structural proteins showed that mitochondrial number and size were increased in ID OLGs, while an increased number of smaller mitochondria was observed in ID ASTs. These results reflect an unfavorable bioenergetic scenario in which ID OLGs fail to progress to a myelinating state, and indicate that the regulation of cell metabolism may impact cell fate decisions and maturation.
ISSN:0893-7648
1559-1182
DOI:10.1007/s12035-022-03149-y