Is Myelin a Metabolic Organelle? Nanoscale Insights into Alzheimer’s Disease
Speaker
Carlos José Matute Almau
Affiliation
EHU
When
Place
CIC nanoGUNE Seminar room, Tolosa Hiribidea 76, Donostia-San Sebastian
Host
Andrey Chuvilin
Myelin is classically viewed as an electrical insulator that enables rapid saltatory conduction along axons. However, accumulating evidence indicates that myelin and oligodendrocytes also play an active role in brain energy metabolism by supporting axonal function through metabolite exchange. In the central nervous system, activity-dependent signaling pathways, including NMDA receptor activation in myelin and oligodendrocytes, promote glucose uptake, glycolysis, and lactate delivery to axons, linking neural activity to local metabolic support.
Given that lipids constitute the vast majority of myelin, this structure may also represent a strategically positioned metabolic reservoir. Consistent with this possibility, we recently showed that marathon running induces a transient and reversible reduction in human brain myelin content, suggesting that myelin participates in dynamic metabolic adaptation under extreme physiological demand. These findings raise the broader question of whether myelin contributes to brain energy homeostasis beyond its established structural and trophic roles.
Addressing this question requires access to the nanoscale organization of myelin and its molecular composition. Here, I will outline a collaborative framework integrating advanced ultrastructural imaging (FIB-SEM) with nanoscale molecular mapping (SNOM) to interrogate myelin architecture in Alzheimer’s disease. I will present the conceptual basis of this approach and discuss initial observations from ongoing work, highlighting how nanoscale imaging may uncover previously unrecognized aspects of myelin function in health and disease.
Together, this work aims to reposition myelin from a passive structural element to a dynamic component of brain metabolism, opening new perspectives for understanding neurodegenerative disease.
Funding: Ministerio de Ciencia e Innovación, CIBERNED, Gobierno Vasco
About the speaker
Carlos Matute trained in physics and neuroscience at the University of Zaragoza, followed by postdoctoral work at the Brain Research Institute of the University of Zürich (with Michel Cuénod and Peter Streit) and at the University of California, Irvine (with Ricardo Miledi). He has also held visiting positions at the Max Planck Institute for Biophysical Chemistry (Göttingen) and the Albert Einstein College of Medicine (New York).
He is Professor of Neuroscience at the University of the Basque Country (UPV/EHU), a member of CIBERNED and IIS Biobizkaia, and founder and former Scientific Director of the Achucarro Basque Center for Neuroscience. He is also Adjunct Professor at Chengdu University of Traditional Chinese Medicine. He is a member of Academia
Europaea, President of the Spanish Society for Neuroscience (SENC), and Secretary General of Network Glia.
His research has focused on the biology of glial cells in health and disease, with seminal contributions to understanding how neurotransmitter signaling regulates oligodendrocyte function and survival. His current work explores myelin as a dynamic and potentially metabolic structure, combining human physiology, advanced imaging, and disease models to investigate its role in brain energy homeostasis and neurodegeneration.