Department of Pathology, Normandy Centre for Genomic and Personalized Medicine, Laboratoire d'Anatomie Pathologique, Pavillon Jacques Delarue, CHU, Normandie Univ, UNIROUEN, INSERM U1245 and Rouen University Hospital, 1 Rue de Germont, 76031, Rouen Cedex, France.
UNIROUEN, INSERM U1245 F76000, Normandy Centre for Genomic and Personalized Medicine, Normandie Univ, Rouen, France.
Acta Neuropathol Commun. 2022 May 14;10(1):74. doi: 10.1186/s40478-022-01378-9.
Prenatal alcohol exposure is a major cause of neurobehavioral disabilities. MRI studies in humans have shown that alcohol is associated with white matter microstructural anomalies but these studies focused on myelin abnormalities only after birth. Only one of these studies evaluated oligodendrocyte lineage, but only for a short period during human foetal life. As data are lacking in humans and alcohol is known to impair oligodendrocyte differentiation in rodents, the present study aimed to compare by immunohistochemistry the oligodendrocyte precursor cells expressing PDGFR-α and immature premyelinating/mature oligodendrocytes expressing Olig2 in the ganglionic eminences and the frontal cortex of 14 human foetuses exposed to alcohol from 15 to 37 weeks' gestation with age-matched controls. The human brains used in this study were obtained at the time of foetal autopsies for medical termination of pregnancy, in utero or post-natal early death. Before birth, PDGFR-α expression was strongly increased in the ganglionic eminences and the cortex of all foetuses exposed to alcohol except at the earliest stage. No massive generation of Olig2 immunoreactive cells was identified in the ganglionic eminences until the end of pregnancy and the density of Olig2-positive cells within the cortex was consistently lower in foetuses exposed to alcohol than in controls. These antenatal data from humans provides further evidence of major oligodendrocyte lineage impairment at specific and key stages of brain development upon prenatal alcohol exposure including defective or delayed generation and maturation of oligodendrocyte precursors.
产前酒精暴露是神经行为障碍的主要原因。人类的 MRI 研究表明，酒精与脑白质微观结构异常有关，但这些研究仅关注出生后髓鞘异常。其中只有一项研究评估了少突胶质细胞谱系，但仅在人类胎儿生命的短暂时期内进行。由于人类缺乏数据，并且已知酒精会损害啮齿动物的少突胶质细胞分化，因此本研究旨在通过免疫组织化学比较 14 名在妊娠 15 至 37 周时暴露于酒精的人类胎儿的神经节隆起和额叶中表达 PDGFR-α 的少突胶质前体细胞和表达 Olig2 的未成熟前髓鞘形成/成熟少突胶质细胞，与年龄匹配的对照组进行比较。本研究中使用的人脑是在因医学原因终止妊娠、宫内或产后早期死亡的胎儿尸检时获得的。在出生前，除了最早的阶段外，所有暴露于酒精的胎儿的神经节隆起和皮质中 PDGFR-α 的表达均强烈增加。直到妊娠末期，神经节隆起中才出现大量的 Olig2 免疫反应性细胞，并且暴露于酒精的胎儿皮质内 Olig2 阳性细胞的密度始终低于对照组。这些来自人类的产前数据提供了进一步的证据，证明产前酒精暴露会在特定和关键的大脑发育阶段对少突胶质细胞谱系造成严重损害，包括少突胶质前体细胞的产生和成熟受损或延迟。
