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.
摘要:
在生命早期暴露于逆境似乎会影响白质的发展,尤其是少突胶质细胞.此外,在经历早期逆境的发育过程中,髓鞘形成发生了改变。在这次审查中,应用两种成熟的早期生活逆境动物模型的研究,即母体分离和母体免疫激活,讨论了少突胶质细胞改变及其对精神疾病的影响。研究表明,少突胶质细胞表达改变导致髓鞘形成减少。此外,早期逆境与细胞死亡增加有关,更简单的形态,并抑制少突胶质细胞成熟。然而,这些效应似乎是区域特异性的,因为一些脑区显示表达增加,而另一些则显示少突胶质细胞相关基因的表达减少,它们尤其发生在正在发展的地区。一些研究还表明,早期逆境会导致少突胶质细胞的过早分化。重要的是,尤其是早期暴露会导致更强的少突胶质细胞相关损伤。然而,由此产生的改变不仅限于出生前和出生后早期的暴露,因为断奶后的社会隔离会导致成年后少突胶质细胞的节间和分支减少,过程变短。最终,发现的改变可能导致与精神疾病相关的脑结构发育的功能障碍和持久改变.迄今为止,只有很少的临床前研究关注早期逆境对少突胶质细胞的影响。需要进行更多的研究,包括几个发育阶段,以进一步阐明少突胶质细胞在精神疾病发展中的作用。