Lame Ducks or Fierce Creatures? - The Role of Oligodendrocytes in Multiple Sclerosis

Abstract

In the pathogenesis of multiple sclerosis (MS), oligodendrocytes and its myelin sheaths are thought to be the primary target of destruction. The mechanism leading to oligodendrocyte injury and demyelination is still elusive. Oligodendrocytes are maintaining up to 50 internodes of myelin, which is an extraordinary metabolic demand. This makes them one of the most vulnerable cell types in the central nervous system (CNS), and even small insults can lead to oligodendrocyte impairment, demyelination, and axonal dysfunction. For this reason, oligodendrocytes are viewed as more or less the "lame ducks" of the CNS who can easily become victims. However, recent data demonstrate that this perception possibly needs to be revised. The latest data suggest that oligodendrocytes may also act as "fierce creatures," influencing the surrounding cells in many ways to preserve its own, as well as their function, allowing sustained functionality of the CNS upon an attack. In this review, the concept of "reactive or activated oligodendrocyte" is introduced, describing alterations in oligodendrocytes which are either protective mechanisms allowing survival in otherwise lethal environment or influence and possibly modulate the ongoing inflammation. Although "harnessed", oligodendrocytes might actively modulate and shape their environment and be part of the immune privilege of the brain.

Subplate in a rat model of preterm hypoxia-ischemia

“…Similarly, at least in moderate cases, astrocytes appeared to be mainly present in the white matter and the deep layers including subplate and absent from the upper layers. The increased vulnerability of the lower cortical layers is in line with previous studies on comparable models of P2 and P3 rats where columns of degenerated cells in the deep cortex involving subplate, layer VI, and layer V were described 17,18…”

Neuroinflammation and Endoplasmic Reticulum Stress Are Coregulated by Crocin To Prevent Demyelination and Neurodegeneration

“…Oligodendrocytes are the principal target cell in EAE (and MS), frequently dying during neuroinflammation and demyelination (55). Microglia and astrocytes maintain homeostasis within the CNS during health; however, they also mediate very specific disease mechanisms as illustrated in Alexander's disease in which GFAP polymorphisms result in demyelination, neurodegeneration, and delayed development (56,57) or HIV-associated encephalopathy during which microglia/macrophages and astrocytes are infected by HIV-1, resulting in neuroinflammation with axonal loss (58,59).…”

Quantitative temporal proteomic analysis of human embryonic stem cell differentiation into oligodendrocyte progenitor cells

“…For instance, several laboratories have identified changes in the gene and protein expression in schizophrenic 51 and multiple sclerosis (MS) patients 40 . While the role of oligodendrocytes injury in MS is well established 52 numerous lines of evidence implicate the role oligodendrocyte injury in the loss of connectivity associated with Schizophrenia 41, 51 . These studies have included comparisons of both transcriptome and proteomic alterations which have identified several oligodendrocyte-related proteins in the progression of disease that were also found here including CNP, TF, QK1, and GSN 41, 51 .…”