Venue: Unité 1034 –
1 avenue de Magellan – Pessac
https://maps.app.goo.gl/neuEkruFjnJNmsu58
Sarah Moyon, PhD
Aix-Marseille University, France
https://www.linkedin.com/in/sarah-moyon-a7710619/
https://inp.univ-amu.fr/fr/annuaire/sarah-moyon
Invited by Candice Chapouly
Biology of Cardiovascular Diseases
https://u1034.bordeaux.inserm.fr/
Title
Epigenetic regulation of neuroglial communication in adaptive myelination and in age-related cognitive decline
Abstract
Aging is associated with progressive cognitive decline, partly linked to impaired myelin plasticity and adaptive myelination. Oligodendrocytes (OLs), the myelinating cells of the central nervous system, support neuronal function through axonal insulation and metabolic coupling. With age, myelin integrity and the capacity to generate new myelin decrease, contributing to cognitive deficits. Emerging evidence indicates that intrinsic oligodendroglial alterations, including epigenetic dysregulation, underlie these defects. In particular, downregulation of the epigenetic activator TET1 alters genes involved in neuroglial communication and the axon–myelin interface.
We have identified SLC12A2, a Na+/K+/Cl- symporter localized at the neuroglial interface, as downregulated in aged oligodendroglial cells. Reduced SLC12A2 expression is associated with structural abnormalities at the axon–myelin interface and impaired motor learning. Using an inducible oligodendrocyte-specific Slc12a2 knockout mouse model, we show that SLC12A2 loss leads to motor learning deficits. In vitro, Slc12a2-deficient OLs display reduced branching and decreased axon–myelin contact, suggesting impaired differentiation and myelination.
This project aims to define how TET1-dependent regulation of SLC12A2 controls neuroglial communication, thus myelin plasticity, during aging and in age-related diseases.