Scientists Uncover How Glucose Influences Myelin Formation and Function

The brain's wiring may depend on something as simple and as powerful as sugar levels. New research from the CUNY Graduate Center reveals that glucose is not just fuel for the brain but a key signal that directs how critical support cells develop during early life.

Published in Nature Neuroscience, the study shows that fluctuations in brain glucose levels help determine whether stem-like cells called oligodendrocyte progenitor cells (OPCs) continue to multiply or mature into oligodendrocytes, the cells responsible for forming myelin. Myelin is the protective sheath around nerve fibers that enables fast and efficient communication between brain cells, essential for milestones like movement, speech, and coordination.

Using advanced imaging techniques, researchers mapped glucose distribution in developing mouse brains and found a striking pattern. Regions with higher glucose levels contained actively dividing progenitor cells, while areas with lower glucose levels showed cells transitioning into myelin-producing forms.

At the center of this mechanism is an enzyme called ATP-citrate lyase (ACLY), which converts glucose into molecules that activate genes required for cell growth. When scientists removed ACLY in experimental models, progenitor cells struggled to multiply, leading to reduced myelin formation. However, the brain showed resilience—mature cells adapted by using alternative energy sources, such as ketone bodies, to continue producing myelin.

Remarkably, when these models were placed on a ketogenic diet, which increases ketone levels, myelin production improved. This finding highlights the brain’s metabolic flexibility and suggests new ways to support development when glucose pathways are disrupted.

The implications extend beyond early development. Conditions like multiple sclerosis, which involve myelin loss, could potentially benefit from therapies targeting these metabolic pathways.

Overall, the study reframes how scientists view brain development—showing that metabolism doesn’t just power the brain, it actively shapes its structure and function.

REFERENCE: Sauma, S., et al. (2026). Glucose-dependent spatial and temporal modulation of oligodendrocyte progenitor cell proliferation via ACLY-regulated histone acetylation. Nature Neuroscience. DOI: 10.1038/s41593-026-02263-7. https://www.nature.com/articles/s41593-026-02263-7