Epigenetic mechanisms of the maternal hyperhomocysteinemia influence on the placenta functional state and the offspring nervous system plasticity

Abstract

According to modern concepts, the susceptibility to certain diseases, especially to cognitive and neuropsychiatric disorders, can be formed during the period of embryonic development. Adverse factors that affect the mother during pregnancy increase the risk of the pathology development in the postnatal period. Despite the relationship found between elevated maternal blood levels of the amino acid homocysteine (Hcy) and fetal brain formation impairments, as well as cognitive deficits in offspring, the role of brain plasticity in the development of these pathologies is still insufficiently studied. This review allows to be acquainted with the available data on the negative impact of hyperhomocysteinemia (HHcy) on the neural plasticity. An important aspect of the problem considered in the review is the possible influence of maternal HHcy on the offspring brain plasticity through the epigenetic mechanisms. Data on changes in intracellular methylation potential, activity of DNA methyltransferases, and DNA methylation in brain cells under the influence of HHcy are presented, and possible effects of HHcy on histone modifications and microRNA expression are considered. Since placenta plays a key role in the transport of nutrients and modulation of signals from mother to fetus, its dysfunction due to epigenetic mechanisms disturbances may affect the development of the fetal CNS. In this regard, the review presents data on the impact of maternal HHcy on the epigenetic regulation in the placenta. The data presented in the review are not only of theoretical significance, but are also of interest for understanding the role of epigenetic mechanisms in the pathogenesis of diseases for which HHcy is a risk factor (pregnancy pathologies accompanied by delayed fetal brain development, cognitive impairments in childhood and neuropsychiatric and neurodegenerative disorders later in life), as well as the search for approaches to their prevention using neuroprotectors.