Oligodendrocytes matter: a review of animal studies on early adversity

Abstract

Exposure to adversities in early life appears to affect the development of white matter, especially oligodendrocytes. Furthermore, altered myelination is present in regions subjected to maturation during the developmental time when early adversities are experienced. In this review, studies applying two well-established animal models of early life adversity, namely maternal separation and maternal immune activation, focusing on oligodendrocyte alterations and resulting implications for psychiatric disorders are discussed. Studies revealed that myelination is reduced as a result of altered oligodendrocyte expression. Furthermore, early adversity is associated with increased cell death, a simpler morphology, and inhibited oligodendrocyte maturation. However, these effects seem to be region- specific as some brain regions show increased expression while others show decreased expression of oligodendroglia-related genes, and they occur especially in regions of ongoing development. Some studies furthermore suggest that early adversity leads to premature differentiation of oligodendrocytes. Importantly, especially early exposure results in stronger oligodendrocyte-related impairments. However, resulting alterations are not restricted to exposure during the early pre- and postnatal days as social isolation after weaning leads to fewer internodes and branches and shorter processes of oligodendrocytes in adulthood. Eventually, the found alterations may lead to dysfunction and long-lasting alterations in structural brain development associated with psychiatric disorders. To date, only few preclinical studies have focused on the effects of early adversity on oligodendrocytes. More studies including several developmental stages are needed to further disentangle the role of oligodendrocytes in the development of psychiatric disorders.

Keywords: Hemispheric asymmetry; Myelinization; Neurodevelopmental; Neuronal maturation; Psychiatry; White matter.

Fig. 1

Different animal models of early adversity (A) lead to alterations in oligodendrocytes in the developing offspring (B). Early stress seems to affect oligodendrocyte maturation and alters the normal proportion of oligodendrocyte precursor cells and oligodendrocytes during development. Stress may also result in less complex oligodendrocyte morphology. The Figure was partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license, the rat image is modified from Mostafa Elturkey from Pixabay