Osmotic Demyelination: From an Oligodendrocyte to an Astrocyte Perspective

Abstract

Osmotic demyelination syndrome (ODS) is a disorder of the central myelin that is often associated with a precipitous rise of serum sodium. Remarkably, while the myelin and oligodendrocytes of specific brain areas degenerate during the disease, neighboring neurons and axons appear unspoiled, and neuroinflammation appears only once demyelination is well established. In addition to blood‒brain barrier breakdown and microglia activation, astrocyte death is among one of the earliest events during ODS pathology. This review will focus on various aspects of biochemical, molecular and cellular aspects of oligodendrocyte and astrocyte changes in ODS-susceptible brain regions, with an emphasis on the crosstalk between those two glial cells. Emerging evidence pointing to the initiating role of astrocytes in region-specific degeneration are discussed.

Keywords: astrocytes; myelin loss; myelinolysis; oligodendrocytes; osmotic demyelination syndrome.

Figure 1

Astrocytopathy during osmotic demyelination. Major changes observed in astrocytes of demyelinating-prone regions include: downregulation of gap junctions (Cx30 and Cx43) [44,48], dysregulation of aquaporin expression (AQP1 and AQP4) [113], ER stress and activation of ER-associated degradation (ERAD) pathway [112], intracytoplasmic aggregates [112,114], swelling of various organelles [44,46,114], loss of GFAP intermediate filaments [6,48], clasmatodendrosis [114], nuclear condensation and upregulation of cell death markers [44,48,72,112].