The Glial Coupling in the Developing Brain: Astrocytes, Oligodendrocytes and Myelin Formation
4 affiliations
- 1Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Morther-Child Health, University of Genoa, 16132 Genoa, Italy
- 2Neonatal Intensive Care Unit, IRCCS Istituto Giannina Gaslini, 16132 Genoa, Italy
- 3Core Facilities—Clinical Proteomics and Metabolomics Unit, IRCCS Istituto Giannina Gaslini, 16132 Genoa, Italy
- 4Pediatric Neurology and Muscular Disease Unit, IRCCS Istituto Giannina Gaslini, 16132 Genoa, Italy
Abstract
Astrocytes and oligodendrocytes contribute to the metabolic, homeostatic and structural organization of the developing brain, yet their interactions evolve across development and remain incompletely characterized during the earliest stages of life. This narrative review examines astrocyte–oligodendrocyte coupling in relation to myelin development and addresses the question of which cellular and metabolic mechanisms support oligodendrocyte maturation and white-matter metabolism before mature astrocytic functions are fully established. Evidence from preterm and ill term neonates is considered together with experimental and adult or elderly studies used exclusively for secondary mechanistic comparison. Astrocytes and oligodendrocytes participate in interconnected metabolic, developmental and homeostatic processes, while perinatal white-matter injury may combine reactive astrogliosis, pre-oligodendrocyte injury and maturation arrest. Neuroimaging, including quantitative susceptibility mapping, synthetic MRI, cranial ultrasound and molecular or myelin-sensitive imaging, provides complementary but indirect information on the structural and maturational consequences of these processes, whereas omics approaches may characterize their molecular environment. Radiomics similarly provides indirect tissue-level biomarkers rather than cell-specific measures of glial biology. Dysglycaemia further illustrates the dependence of developing white matter on coordinated cellular energy handling and the potential relevance of immature astrocyte–oligodendrocyte interactions during metabolic instability. Evidence from very early development suggests that oligodendrocyte maturation occurs within a changing cellular environment in which astroglial maturation, neuronal and vascular processes, and immune and metabolic mechanisms coexist. The Crossword and Foil Effects are proposed as hypothesis-generating frameworks to organize these intersecting developmental, metabolic, cellular, imaging and molecular dimensions rather than as experimentally validated causal models. Overall, no single cellular substitute for mature astrocytic functions is identified; instead, oligodendrocyte maturation appears to emerge within a developmentally changing division of metabolic, homeostatic and signaling labour across astroglial, neuronal, vascular and immune compartments.
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BibTeX
@article{canepa2026glial,
title = {{The Glial Coupling in the Developing Brain: Astrocytes, Oligodendrocytes and Myelin Formation}},
author = {Maria Ester Canepa and Chiara Santucci and Daiana Mariano and Sara Mangini and Andrea Calandrino and Luigi Gagliardi and Andrea Petretto and Pasquale Striano and Luca Antonio Ramenghi},
journal = {Metabolites},
year = {2026},
month = oct,
doi = {10.3390/metabo16100774},
url = {https://www.mdpi.com/2218-1989/16/10/774},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The Glial Coupling in the Developing Brain: Astrocytes, Oligodendrocytes and Myelin Formation
AU - Maria Ester Canepa
AU - Chiara Santucci
AU - Daiana Mariano
AU - Sara Mangini
AU - Andrea Calandrino
AU - Luigi Gagliardi
AU - Andrea Petretto
AU - Pasquale Striano
AU - Luca Antonio Ramenghi
PY - 2026
DA - 2026/10/13
JO - Metabolites
DO - 10.3390/metabo16100774
UR - https://www.mdpi.com/2218-1989/16/10/774
AB - Astrocytes and oligodendrocytes contribute to the metabolic, homeostatic and structural organization of the developing brain, yet their interactions evolve across development and remain incompletely characterized during the earliest stages of life. This narrative review examines astrocyte–oligodendrocyte coupling in relation to myelin development and addresses the question of which cellular and metabolic mechanisms support oligodendrocyte maturation and white-matter metabolism before mature astrocytic functions are fully established. Evidence from preterm and ill term neonates is considered together with experimental and adult or elderly studies used exclusively for secondary mechanistic comparison. Astrocytes and oligodendrocytes participate in interconnected metabolic, developmental and homeostatic processes, while perinatal white-matter injury may combine reactive astrogliosis, pre-oligodendrocyte injury and maturation arrest. Neuroimaging, including quantitative susceptibility mapping, synthetic MRI, cranial ultrasound and molecular or myelin-sensitive imaging, provides complementary but indirect information on the structural and maturational consequences of these processes, whereas omics approaches may characterize their molecular environment. Radiomics similarly provides indirect tissue-level biomarkers rather than cell-specific measures of glial biology. Dysglycaemia further illustrates the dependence of developing white matter on coordinated cellular energy handling and the potential relevance of immature astrocyte–oligodendrocyte interactions during metabolic instability. Evidence from very early development suggests that oligodendrocyte maturation occurs within a changing cellular environment in which astroglial maturation, neuronal and vascular processes, and immune and metabolic mechanisms coexist. The Crossword and Foil Effects are proposed as hypothesis-generating frameworks to organize these intersecting developmental, metabolic, cellular, imaging and molecular dimensions rather than as experimentally validated causal models. Overall, no single cellular substitute for mature astrocytic functions is identified; instead, oligodendrocyte maturation appears to emerge within a developmentally changing division of metabolic, homeostatic and signaling labour across astroglial, neuronal, vascular and immune compartments.
SN - 2218-1989
ER -