D.O. Ott Institute of Obstetrics, Gynecology, and Reproductology, St. Petersburg, Russia.
I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russia.
Neurotox Res. 2020 Aug;38(2):408-420. doi: 10.1007/s12640-020-00233-w. Epub 2020 Jun 5.
Maternal hyperhomocysteinemia is one of the common complications of pregnancy that causes offspring cognitive deficits during postnatal development. In the present work, we evaluated the effect of prenatal hyperhomocysteinemia on structural and ultrastructural organization, neuronal and glial cell number, apoptosis (caspase-3 content and activity), inflammatory markers (tumor necrosis factor-α, interleukin-6, and interleukin-1β), and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation in the offspring brain cortex in early ontogenesis. Wistar female rats received methionine (0.6 g/kg body weight) by oral administration during pregnancy. Histological and biochemical analyses of 5- and 20-day-old pups' cortical tissue were performed. Lysosome accumulation and other neurodegenerative changes in neurons of animals with impaired embryonic development were investigated by electron microscopy. Neuronal staining (anti-NeuN) revealed a reduction in neuronal number, accompanied by increasing of caspase-3 active form protein level and activity. Maternal hyperhomocysteinemia also elevated the number of astroglial and microglial cells and increased expression of interleukin-1β and p38 MAPK phosphorylation, which indicates the development of neuroinflammatory processes.
母体高同型半胱氨酸血症是妊娠的常见并发症之一，可导致后代在出生后发育过程中出现认知缺陷。在本工作中，我们评估了产前高同型半胱氨酸血症对后代大脑皮质在早期发生过程中的结构和超微结构组织、神经元和神经胶质细胞数量、细胞凋亡（半胱天冬酶-3 含量和活性）、炎症标志物（肿瘤坏死因子-α、白细胞介素-6 和白细胞介素-1β）以及 p38 丝裂原活化蛋白激酶（p38 MAPK）磷酸化的影响。Wistar 雌性大鼠在怀孕期间通过口服给予蛋氨酸（0.6 g/kg 体重）。对 5 天和 20 天龄幼崽皮质组织进行了组织学和生化分析。通过电子显微镜研究了胚胎发育受损动物神经元中溶酶体积累和其他神经退行性变化。神经元染色（抗 NeuN）显示神经元数量减少，同时半胱天冬酶-3 活性形式蛋白水平和活性增加。母体高同型半胱氨酸血症还增加了星形胶质细胞和小胶质细胞的数量，并增加了白细胞介素-1β和 p38 MAPK 磷酸化的表达，这表明神经炎症过程的发展。
