Myelin is a sheath around the nerves made by certain brain cells called oligodendrocytes. These cells arise from progenitor cells called oligodendrocyte Progenitor Cells (OPCs). Myelination begins before birth and persists into adulthood, assisting the brain and body in reaching critical developmental milestones, including sitting up, crawling, walking, and talking.
For decades, neuroscientists have been intrigued by what makes postnatal OPCs survive, proliferate, or differentiate. Now researchers are suggesting the answer might be something deceptively straightforward: sugar.
In a new study at the Advanced Science Research Center at the CUNY Graduate Center (CUNY ASRC), researchers have found that glucose fluctuations and changes in blood vessel growth act as fine-tuners of Oligodendrocyte Precursor Cell (OPC) populations. Regions of high glucose demonstrate elevated OPC proliferation and higher levels of histone acetylation, the genetic “on switch”, by the ATP‑citrate lyase (ACLY) enzyme. This enzyme converts glucose‑derived citrate into acetyl‑CoA, the source of all gene regulation.
The team used advanced technology to map glucose levels across developing mouse brains. It has been found that glucose levels in the brain are region- and time-dependent. OPCs were more likely to divide and proliferate in areas with higher glucose levels. OPCs were more likely to begin differentiating into oligodendrocytes, the myelin-producing cells, in areas with lower glucose levels.
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Sami Sauma, a postdoctoral researcher with the CUNY ASRC Neuroscience Initiative who received his Ph.D. from the Graduate Center, said, “Our findings show that glucose is not just fuel for the brain, it’s also a signal for the cells to divide. We found that when glucose levels are high in a particular brain region, progenitors use it to drive proliferation. As glucose levels shift, the same cells switch gears and begin maturing. It’s a beautifully coordinated metabolic system that helps shape brain development.”
When researchers deleted Acly in OPCs in mice, the animals briefly developed hypomyelination, with too few OPCs to keep pace with demand. Nevertheless, differentiation into mature oligodendrocytes persisted with the help of a smart metabolic bypass: other enzymes outside the nucleus were named to make acetyl‑CoA from non‑glucose sources.
The image represents the distribution of distinct metabolites in brain sections, using MALDI Imaging. The relative amount of each metabolite is represented by a color scale.
Credit: Sami Sauma
It found that labor is distributed astonishingly. While OPCs rely on ACLY‑driven nuclear acetyl‑CoA from glucose to control proliferation, mature oligodendrocytes have high levels of extranuclear acetyl‑CoA from non-carbohydrate substrates for myelin production.
Patrizia Casaccia, founding director of the CUNY ASRC Neuroscience Initiative and Einstein Professor of Biology at the CUNY Graduate Center, said, “This study reveals that the same cell lineage interprets different metabolic signals at distinct stages of development. By understanding how glucose and alternative energy sources regulate proliferation and myelin formation, we are uncovering new metabolic strategies that could be harnessed to protect myelin in the developing brain and even promote repair in disease states.”
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This metabolic choreography suggests that the brain’s wiring system is tuned not only by genetic programs but also by the ebb and flow of nutrients. In other words, glucose isn’t just fuel; it’s a conductor, orchestrating when progenitor cells multiply and when they commit to becoming the insulating engineers of the nervous system.
The findings may have important implications for neurological disorders marked by myelin loss, such as multiple sclerosis. By targeting the metabolic pathways that control whether progenitor cells multiply or mature into myelin‑producing oligodendrocytes, scientists could design new therapies to boost myelin repair.
Journal Reference:
Sauma, S., Stransky, S., Selcen, I. et al. Glucose-dependent spatial and temporal modulation of oligodendrocyte progenitor cell proliferation via ACLY-regulated histone acetylation. Nat Neurosci (2026). DOI: 10.1038/s41593-026-02263-7