Shaw Julia C, Crombie Gabrielle K, Palliser Hannah K, Hirst Jonathan J
School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.
Mothers and Babies Research Centre, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia.
Front Pediatr. 2021 Feb 4;9:618052. doi: 10.3389/fped.2021.618052. eCollection 2021.
Preterm birth is associated with poor long-term neurodevelopmental and behavioral outcomes, even in the absence of obvious brain injury at the time of birth. In particular, behavioral disorders characterized by inattention, social difficulties and anxiety are common among children and adolescents who were born moderately to late preterm (32-37 weeks' gestation). Diffuse deficits in white matter microstructure are thought to play a role in these poor outcomes with evidence suggesting that a failure of oligodendrocytes to mature and myelinate axons is responsible. However, there remains a major knowledge gap over the mechanisms by which preterm birth interrupts normal oligodendrocyte development. neurodevelopment occurs in an inhibitory-dominant environment due to the action of placentally derived neurosteroids on the GABA receptor, thus promoting GABAergic inhibitory activity and maintaining the fetal behavioral state. Following preterm birth, and the subsequent premature exposure to the environment, this action of neurosteroids on GABA receptors is greatly reduced. Coinciding with a reduction in GABAergic inhibition, the preterm neonatal brain is also exposed to environmental insults such as periods of hypoxia and excessive glucocorticoid concentrations. Together, these insults may increase levels of the excitatory neurotransmitter glutamate in the developing brain and result in a shift in the balance of inhibitory: excitatory activity toward excitatory. This review will outline the normal development of oligodendrocytes, how it is disrupted under excitation-dominated conditions and highlight how shifting the balance back toward an inhibitory-dominated environment may improve outcomes.
早产与不良的长期神经发育和行为后果相关，即使在出生时没有明显的脑损伤。特别是，以注意力不集中、社交困难和焦虑为特征的行为障碍在中度至晚期早产（妊娠32 - 37周）出生的儿童和青少年中很常见。白质微结构的弥漫性缺陷被认为在这些不良后果中起作用，有证据表明少突胶质细胞成熟和轴突髓鞘形成失败是其原因。然而，关于早产中断正常少突胶质细胞发育的机制仍存在重大知识空白。由于胎盘来源的神经甾体对GABA受体的作用，神经发育发生在以抑制为主的环境中，从而促进GABA能抑制活性并维持胎儿行为状态。早产及随后过早暴露于外界环境后，神经甾体对GABA受体的这种作用会大大降低。与GABA能抑制的减少同时发生的是，早产新生儿脑还会暴露于外界环境损伤，如缺氧期和糖皮质激素浓度过高。这些损伤共同作用可能会增加发育中大脑中兴奋性神经递质谷氨酸的水平，并导致抑制性：兴奋性活动平衡向兴奋性方向转变。本综述将概述少突胶质细胞的正常发育、在兴奋主导条件下其如何被破坏，并强调将平衡转向抑制主导环境可能如何改善结局。
