Ott Research Institute of Obstetrics, Gynecology and Reproductive Medicine, St. Petersburg, 199034, Russia.
St. Petersburg Institute of Bioregulation and Gerontology, St. Petersburg, 197110, Russia.
Biochemistry (Mosc). 2023 Apr;88(4):435-456. doi: 10.1134/S0006297923040016.
According to modern view, susceptibility to diseases, specifically to cognitive and neuropsychiatric disorders, can form during embryonic development. Adverse factors affecting mother during the pregnancy increase the risk of developing pathologies. Despite the association between elevated maternal blood homocysteine (Hcy) and fetal brain impairments, as well as cognitive deficits in the offspring, the role of brain plasticity in the development of these pathologies remains poorly studied. Here, we review the data on the negative impact of hyperhomocysteinemia (HHcy) on the neural plasticity, in particular, its possible influence on the offspring brain plasticity through epigenetic mechanisms, such as changes in intracellular methylation potential, activity of DNA methyltransferases, DNA methylation, histone modifications, and microRNA expression in brain cells. Since placenta plays a key role in the transport of nutrients and transmission of signals from mother to fetus, its dysfunction due to aberrant epigenetic regulation can affect the development of fetal CNS. The review also presents the data on the impact of maternal HHcy on the epigenetic regulation in the placenta. The data presented in the review are not only interesting from purely scientific point of view, but can help in understanding the role of HHcy and epigenetic mechanisms in the pathogenesis of diseases, such as pregnancy pathologies resulting in the delayed development of fetal brain, cognitive impairments in the offspring during childhood, and neuropsychiatric and neurodegenerative disorders later in life, as well as in the search for approaches for their prevention using neuroprotectors.
根据现代观点，疾病易感性，特别是认知和神经精神障碍，可能在胚胎发育过程中形成。在妊娠期间影响母亲的不利因素会增加发生病理的风险。尽管母体血液同型半胱氨酸（Hcy）升高与胎儿脑损伤以及后代认知缺陷之间存在关联，但脑可塑性在这些病理发展中的作用仍研究甚少。在这里，我们综述了高同型半胱氨酸血症（HHcy）对神经可塑性的负面影响的数据，特别是其通过表观遗传机制对后代脑可塑性的可能影响，例如细胞内甲基化潜能、DNA 甲基转移酶活性、DNA 甲基化、组蛋白修饰和脑细胞中 microRNA 表达的变化。由于胎盘在营养物质的运输和母体向胎儿信号的传递中起着关键作用，其异常的表观遗传调节会影响胎儿中枢神经系统的发育。该综述还介绍了母体 HHcy 对胎盘表观遗传调节的影响数据。本综述中呈现的数据不仅从纯科学角度来看很有趣，而且有助于理解 HHcy 和表观遗传机制在妊娠病理导致胎儿脑发育迟缓、儿童期后代认知障碍以及晚年神经精神和神经退行性疾病发病机制中的作用，以及寻找使用神经保护剂预防这些疾病的方法。
