Glucose Levels Act as a Master Switch for Brain Myelin Formation
Key Discovery: Researchers found that low brain glucose signals stem-like cells to mature into myelin-forming cells, while high glucose keeps them in a proliferative state.
A new study from the Advanced Science Research Center (ASRC) at the CUNY Graduate Center has revealed that glucose in the brain functions as more than just fuel—it acts as a critical biological signal. Set for publication in Nature Neuroscience, the research demonstrates that fluctuating glucose levels directly determine whether progenitor cells divide or mature into myelin-forming oligodendrocytes.
Mapping Sugar in the Developing Brain
Using advanced MALDI imaging technology, the team created detailed maps of glucose distribution in developing mouse brains. The results were striking:
- High glucose zones correlated with areas where progenitor cells were actively proliferating.
- Low glucose zones correlated with regions where cells were maturing into oligodendrocytes.
The developmental window studied corresponds to approximately 32–40 weeks of human gestation, a critical period when premature infants are particularly vulnerable to white matter injury.
The Enzymatic Gatekeeper: ATP-Citrate Lyase
The study identified the enzyme ATP-citrate lyase (ACLY) as central to this process. ACLY converts glucose-derived molecules into acetyl-CoA within the nucleus, which in turn activates the genes responsible for cell proliferation.
When the team deleted ACLY in oligodendrocyte progenitor cells (OPCs):
- Cell proliferation was significantly reduced.
- The mice developed temporary myelin deficits.
Mature Cells Can Switch Fuel Sources
A remarkable finding was that mature oligodendrocytes are not entirely dependent on glucose. They can utilize alternative fuel sources, such as ketone bodies, to continue producing myelin.
Mice on a ketogenic diet showed improved myelin production despite having the ACLY gene deleted, suggesting a metabolic flexibility that could be exploited therapeutically.
Implications for Human Health
The findings open new avenues for treating several neurological conditions:
- Premature birth complications: Metabolic support during vulnerable developmental windows could protect progenitor cells and myelin.
- Multiple sclerosis: Targeting metabolic pathways might offer a novel therapeutic strategy for demyelinating disorders.
What the Researchers Say
Lead author Sami Sauma, a postdoctoral researcher at CUNY ASRC, stated: "Our findings show that glucose is not just fuel... it's also a signal for the cells to divide."
Patrizia Casaccia, founding director of the CUNY ASRC Neuroscience Initiative, added: "This study reveals that the same cell lineage interprets different metabolic signals at distinct stages of development."
The study was supported by the National Institute of Neurological Disorders and Stroke at the NIH.
DOI: 10.1038/s41593-026-02263-7