Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
Prog Neurobiol. 2021 Jul;202:102054. doi: 10.1016/j.pneurobio.2021.102054. Epub 2021 Apr 24.
The cortex in the mammalian brain is the most complex brain region that integrates sensory information and coordinates motor and cognitive processes. To perform such functions, the cortex contains multiple subtypes of neurons that are generated during embryogenesis. Newly born neurons migrate to their proper location in the cortex, grow axons and dendrites, and form neuronal circuits. These developmental processes in the fetal brain are regulated to a large extent by a great variety of factors derived from the mother - starting from simple nutrients as building blocks and ending with hormones. Thus, when the normal maternal environment is disturbed due to maternal infection, stress, malnutrition, or toxic substances, it might have a profound impact on cortical development and the offspring can develop a variety of neurodevelopmental disorders. Here we first describe the major developmental processes which generate neuronal diversity in the cortex. We then review our knowledge of how most common maternal insults affect cortical development, perturb neuronal circuits, and lead to neurodevelopmental disorders. We further present a concept of selective vulnerability of cortical neuronal subtypes to maternal-derived insults, where the vulnerability of cortical neurons and their progenitors to an insult depends on the time (developmental period), place (location in the developing brain), and type (unique features of a cell type and an insult). Finally, we provide evidence for the existence of selective vulnerability during cortical development and identify the most vulnerable neuronal types, stages of differentiation, and developmental time for major maternal-derived insults.
哺乳动物大脑的皮层是整合感觉信息和协调运动及认知过程的最复杂的脑区。为了执行这些功能，皮层包含在胚胎发生期间产生的多种神经元亚型。新生神经元迁移到皮层的适当位置，生长轴突和树突，并形成神经元回路。胎儿大脑中的这些发育过程在很大程度上受到来自母体的多种因素的调节——从简单的营养物质作为构建块开始，到激素结束。因此，当正常的母体环境因母体感染、压力、营养不良或有毒物质而受到干扰时，可能会对皮层发育产生深远影响，后代可能会发展出多种神经发育障碍。在这里，我们首先描述了产生皮层神经元多样性的主要发育过程。然后，我们回顾了我们对常见母体损伤如何影响皮层发育、扰乱神经元回路以及导致神经发育障碍的认识。我们进一步提出了皮质神经元对母体来源损伤的选择性易损性的概念，其中皮质神经元及其前体细胞对损伤的易感性取决于时间（发育阶段）、地点（发育中大脑的位置）和类型（细胞类型和损伤的独特特征）。最后，我们提供了在皮层发育过程中存在选择性易损性的证据，并确定了主要母体来源损伤的最易受损的神经元类型、分化阶段和发育时间。
