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Epigenetic Mechanisms Involved in the Effects of Maternal Hyperhomocysteinemia on the Functional State of Placenta and Nervous System Plasticity in the Offspring

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Abstract

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.

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Abbreviations

AD:

Alzheimer’s disease

BDNF:

brain-derived neurotrophic factor

DNMT:

DNA methyltransferase

Hcy:

homocysteine

HDAC:

histone deacetylase

HHcy:

hyperhomocysteinemia

IUGR:

intrauterine growth restriction

LINE-1:

long interspersed nuclear element

LTP:

long-term potentiation

MeCP2:

methyl-CpG-binding protein

2; NDD:

neurodegenerative disease

NMDA:

N-methyl-D-aspartate

PE:

preeclampsia

SAH:

S-adenosylhomocysteine

SAM:

S-adenosylmethionine

References

  1. Irvine, N., England-Mason, G., Field, C. J., Dewey, D., and Aghajafari, F. (2022) Prenatal folate and choline levels and brain and cognitive development in children: a critical narrative review, Nutrients, 14, 364, https://doi.org/10.3390/nu14020364.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Naninck, E. F. G., Stijger, P. C., and Brouwer-Brolsma, E. M. (2019) The importance of maternal folate status for brain development and function of offspring, Adv. Nutr., 10, 502-519, https://doi.org/10.1093/advances/nmy120.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Korsmo, H. W., and Jiang, X. (2021) One carbon metabolism and early development: a diet-dependent destiny, Trends Endocrinol. Metab., 32, 579-593, https://doi.org/10.1016/j.tem.2021.05.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Arutjunyan, A. V., Kerkeshko, G. O., Milyutina, Y. P., Shcherbitskaia, A. D., and Zalozniaia, I. V. (2021) Prenatal stress in maternal hyperhomocysteinemia: impairments in the fetal nervous system development and placental function, Biochemistry (Moscow), 86, 716-728, https://doi.org/10.1134/S0006297921060092.

    Article  CAS  PubMed  Google Scholar 

  5. Baydas, G., Koz, S. T., Tuzcu, M., Nedzvetsky, V. S., and Etem, E. (2007) Effects of maternal hyperhomocysteinemia induced by high methionine diet on the learning and memory performance in offspring, Int. J. Dev. Neurosci., 25, 133-139, https://doi.org/10.1016/j.ijdevneu.2007.03.001.

    Article  CAS  PubMed  Google Scholar 

  6. Baydas, G., Koz, S. T., Tuzcu, M., and Nedzvetsky, V. S. (2008) Melatonin prevents gestational hyperhomocysteinemia-associated alterations in neurobehavioral developments in rats, J. Pineal Res., 44, 181-188, https://doi.org/10.1111/j.1600-079X.2007.00506.x.

    Article  CAS  PubMed  Google Scholar 

  7. Koz, S. T., Gouwy, N. T., Demir, N., Nedzvetsky, V. S., Etem, E., and Baydas, G. (2010) Effects of maternal hyperhomocysteinemia induced by methionine intake on oxidative stress and apoptosis in pup rat brain, Int. J. Dev. Neurosci., 28, 325-329, https://doi.org/10.1016/j.ijdevneu.2010.02.006.

    Article  CAS  PubMed  Google Scholar 

  8. Pustygina, A. V., Milyutina, Y. P., Zaloznyaya, I. V., and Arutyunyan, A. V. (2015) Indices of oxidative stress in the brain of newborn rats subjected to prenatal hyperhomocysteinemia, Neurochem. J., 9, 60-65, https://doi.org/10.1134/s1819712415010079.

    Article  CAS  Google Scholar 

  9. Geoffroy, A., Kerek, R., Pourie, G., Helle, D., Gueant, J. L., Daval, J. L., and Bossenmeyer-Pourie, C. (2017) Late maternal folate supplementation rescues from methyl donor deficiency-associated brain defects by restoring Let-7 and miR-34 pathways, Mol. Neurobiol., 54, 5017-5033, https://doi.org/10.1007/s12035-016-0035-8.

    Article  CAS  PubMed  Google Scholar 

  10. Geoffroy, A., Saber-Cherif, L., Pourie, G., Helle, D., Umoret, R., Gueant, J. L., Bossenmeyer-Pourie, C., and Daval, J. L. (2019) Developmental impairments in a rat model of methyl donor deficiency: effects of a late maternal supplementation with folic acid, Int. J. Mol. Sci., 20, 973, https://doi.org/10.3390/ijms20040973.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Arutjunyan, A. V., Milyutina, Y. P., Shcherbitskaia, A. D., Kerkeshko, G. O., Zalozniaia, I. V., and Mikhel, A. V. (2020) Neurotrophins of the fetal brain and placenta in prenatal hyperhomocysteinemia, Biochemistry (Moscow), 85, 248-259, https://doi.org/10.1134/S000629792002008X.

    Article  Google Scholar 

  12. Arutjunyan, A., Kozina, L., Stvolinskiy, S., Bulygina, Y., Mashkina, A., and Khavinson, V. (2012) Pinealon protects the rat offspring from prenatal hyperhomocysteinemia, Int. J. Clin. Exp. Med., 5, 179-185.

    PubMed  PubMed Central  Google Scholar 

  13. Shcherbitskaia, A. D., Vasilev, D. S., Milyutina, Y. P., Tumanova, N. L., Mikhel, A. V., Zalozniaia, I. V., and Arutjunyan, A. V. (2021) Prenatal hyperhomocysteinemia induces glial activation and alters neuroinflammatory marker expression in infant rat hippocampus, Cells, 10, 1536, https://doi.org/10.3390/cells10061536.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Shcherbitskaia, A. D., Vasilev, D. S., Milyutina, Y. P., Tumanova, N. L., Zalozniaia, I. V., Kerkeshko, G. O., and Arutjunyan, A. V. (2020) Maternal hyperhomocysteinemia induces neuroinflammation and neuronal death in the rat offspring cortex, Neurotox Res., 38, 408-420, https://doi.org/10.1007/s12640-020-00233-w.

    Article  CAS  PubMed  Google Scholar 

  15. Jadavji, N. M., Deng, L., Malysheva, O., Caudill, M. A., and Rozen, R. (2015) MTHFR deficiency or reduced intake of folate or choline in pregnant mice results in impaired short-term memory and increased apoptosis in the hippocampus of wild-type offspring, Neuroscience, 300, 1-9, https://doi.org/10.1016/j.neuroscience.2015.04.067.

    Article  CAS  PubMed  Google Scholar 

  16. Saber Cherif, L., Pourie, G., Geoffroy, A., Julien, A., Helle, D., Robert, A., Umoret, R., Gueant, J. L., Bossenmeyer-Pourie, C., and Daval, J. L. (2019) Methyl donor deficiency during gestation and lactation in the rat affects the expression of neuropeptides and related receptors in the hypothalamus, Int. J. Mol. Sci., 20, 5097, https://doi.org/10.3390/ijms20205097.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Schweinberger, B. M., Rodrigues, A. F., Turcatel, E., Pierozan, P., Pettenuzzo, L. F., Grings, M., Scaini, G., Parisi, M. M., Leipnitz, G., Streck, E. L., Barbe-Tuana, F. M., and Wyse, A. T. S. (2018) Maternal hypermethioninemia affects neurons number, neurotrophins levels, energy metabolism, and Na+,K+-ATPase expression/content in brain of rat offspring, Mol. Neurobiol., 55, 980-988, https://doi.org/10.1007/s12035-017-0383-z.

    Article  CAS  PubMed  Google Scholar 

  18. De Crescenzo, A. H., Panoutsopoulos, A. A., Tat, L., Schaaf, Z., Racherla, S., Henderson, L., Leung, K. Y., Greene, N. D. E., Green, R., and Zarbalis, K. S. (2020) Deficient or excess folic acid supply during pregnancy alter cortical neurodevelopment in mouse offspring, Cereb. Cortex, 31, 635-649, https://doi.org/10.1093/cercor/bhaa248.

    Article  Google Scholar 

  19. Li, W., Li, Z., Zhou, D., Zhang, X., Yan, J., and Huang, G. (2019) Maternal folic acid deficiency stimulates neural cell apoptosis via miR-34a associated with Bcl-2 in the rat foetal brain, Int. J. Dev. Neurosci., 72, 6-12, https://doi.org/10.1016/j.ijdevneu.2018.11.002.

    Article  CAS  PubMed  Google Scholar 

  20. Chen, S., Alhassen, W., Yoshimura, R., De Silva, A., Abbott, G. W., Baldi, P., and Alachkar, A. (2020) Metabolomic and transcriptomic signatures of prenatal excessive methionine support nature rather than nurture in schizophrenia pathogenesis, Commun. Biol., 3, 409, https://doi.org/10.1038/s42003-020-01124-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Craciunescu, C. N., Johnson, A. R., and Zeisel, S. H. (2010) Dietary choline reverses some, but not all, effects of folate deficiency on neurogenesis and apoptosis in fetal mouse brain, J. Nutr., 140, 1162-1166, https://doi.org/10.3945/jn.110.122044.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Milyutina, Yu. P., Shcherbitskaya, A. D., Saltykova, E. D., Kozina, L. S., Zhuravin, I. A., Nalivaeva, N. N., and Arutjunyan, A. V. (2017) Metabolic impairments in the placenta and brain of the fetuses of pregnant rats after experimental hyperhomocysteinemia, Ross. Physiol. Zhurn. im. I. M. Sechenova, 103, 1280-1291.

    Google Scholar 

  23. Vasilev, D. S., Shcherbitskaia, A. D., Tumanova, N. L., Mikhel, A. V., Milyutina, Y. P., Kovalenko, A. A., Dubrovskaya, N. M., Inozemtseva, D. B., Zalozniaia, I. V., and Arutjunyan, A. V. (2023) Maternal hyperhomocysteinemia disturbs the mechanisms of embryonic brain development and its maturation in early postnatal ontogenesis, Cells, 12, 189, https://doi.org/10.3390/cells12010189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Blaise, S. A., Nedelec, E., Schroeder, H., Alberto, J. M., Bossenmeyer-Pourie, C., Gueant, J. L., and Daval, J. L. (2007) Gestational vitamin B deficiency leads to homocysteine-associated brain apoptosis and alters neurobehavioral development in rats, Am. J. Pathol., 170, 667-679, https://doi.org/10.2353/ajpath.2007.060339.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Blaise, S. A., Nedelec, E., Alberto, J. M., Schroeder, H., Audonnet, S., Bossenmeyer-Pourie, C., Gueant, J. L., and Daval, J. L. (2009) Short hypoxia could attenuate the adverse effects of hyperhomocysteinemia on the developing rat brain by inducing neurogenesis, Exp. Neurol., 216, 231-238, https://doi.org/10.1016/j.expneurol.2008.11.020.

    Article  CAS  PubMed  Google Scholar 

  26. Shcherbitskaya, A. D., Milyutina, Y. P., Zaloznyaya, I. V., Arutjunyan, A. V., Nalivaeva, N. N., and Zhuravin, I. A. (2017) The effects of prenatal hyperhomocysteinemia on the formation of memory and the contents of biogenic amines in the rat hippocampus, Neurochem. J., 11, 296-301, https://doi.org/10.1134/s1819712417040080.

    Article  CAS  Google Scholar 

  27. Yakovleva, O. V., Ziganshina, A. R., Dmitrieva, S. A., Arslanova, A. N., Yakovlev, A. V., Minibayeva, F. V., Khaertdinov, N. N., Ziyatdinova, G. K., Giniatullin, R. A., and Sitdikova, G. F. (2018) Hydrogen sulfide ameliorates developmental impairments of rat offspring with prenatal hyperhomocysteinemia, Oxid. Med. Cell. Longev., 2018, 2746873, https://doi.org/10.1155/2018/2746873.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Yakovleva, O., Bogatova, K., Mukhtarova, R., Yakovlev, A., Shakhmatova, V., Gerasimova, E., Ziyatdinova, G., Hermann, A., and Sitdikova, G. (2020) Hydrogen sulfide alleviates anxiety, motor, and cognitive dysfunctions in rats with maternal hyperhomocysteinemia via mitigation of oxidative stress, Biomolecules, 10, 995, https://doi.org/10.3390/biom10070995.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gerasimova, E., Burkhanova, G., Chernova, K., Zakharov, A., Enikeev, D., Khaertdinov, N., Giniatullin, R., and Sitdikova, G. (2021) Hyperhomocysteinemia increases susceptibility to cortical spreading depression associated with photophobia, mechanical allodynia, and anxiety in rats, Behav. Brain Res., 409, 113324, https://doi.org/10.1016/j.bbr.2021.113324.

    Article  CAS  PubMed  Google Scholar 

  30. Gerasimova, E., Yakovleva, O., Enikeev, D., Bogatova, K., Hermann, A., Giniatullin, R., and Sitdikova, G. (2022) Hyperhomocysteinemia increases cortical excitability and aggravates mechanical hyperalgesia and anxiety in a nitroglycerine-induced migraine model in rats, Biomolecules, 12, 735, https://doi.org/10.3390/biom12050735.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hassan, Z., Coelho, D., Kokten, T., Alberto, J. M., Umoret, R., Daval, J. L., Gueant, J. L., Bossenmeyer-Pourie, C., and Pourie, G. (2019) Brain susceptibility to methyl donor deficiency: from fetal programming to aging outcome in rats, Int. J. Mol. Sci., 20, 5692, https://doi.org/10.3390/ijms20225692.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Pourie, G., Martin, N., Daval, J. L., Alberto, J. M., Umoret, R., Gueant, J. L., and Bossenmeyer-Pourie, C. (2020) The stimulation of neurogenesis improves the cognitive status of aging rats subjected to gestational and perinatal deficiency of B9-12 vitamins, Int. J. Mol. Sci., 21, 8008, https://doi.org/10.3390/ijms21218008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Figueiro, P.W., de Moreira, D. S., Dos Santos, T. M., Prezzi, C. A., Rohden, F., Faccioni-Heuser, M. C., Manfredini, V., Netto, C. A., and Wyse, A. T. S. (2019) The neuroprotective role of melatonin in a gestational hypermethioninemia model, Int. J. Dev. Neurosci., 78, 198-209, https://doi.org/10.1016/j.ijdevneu.2019.08.004.

    Article  CAS  PubMed  Google Scholar 

  34. Schweinberger, B. M., Rodrigues, A. F., Dos Santos, T. M., Rohden, F., Barbosa, S., da Luz Soster, P. R., Partata, W. A., Faccioni-Heuser, M. C., and Wyse, A. T. S. (2018) Methionine administration in pregnant rats causes memory deficit in the offspring and alters ultrastructure in brain tissue, Neurotox. Res., 33, 239-246, https://doi.org/10.1007/s12640-017-9830-x.

    Article  CAS  PubMed  Google Scholar 

  35. Zhou, D., Li, Z., Sun, Y., Yan, J., Huang, G., and Li, W. (2022) Early life stage folic acid deficiency delays the neurobehavioral development and cognitive function of rat offspring by hindering de novo telomere synthesis, Int. J. Mol. Sci., 23, 6948, https://doi.org/10.3390/ijms23136948.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Degroote, S., Hunting, D., and Takser, L. (2018) Periconceptional folate deficiency leads to autism-like traits in Wistar rat offspring, Neurotoxicol. Teratol., 66, 132-138, https://doi.org/10.1016/j.ntt.2017.12.008.

    Article  CAS  PubMed  Google Scholar 

  37. Makhro, A. V., Mashkina, A. P., Solenaya, O. A., Trunova, O. A., Kozina, L. S., Arutyunian, A. V., and Bulygina, E. R. (2008) Prenatal hyperhomocysteinemia as a model of oxidative stress of the brain, Bull. Exp. Biol. Med., 146, 33-35, https://doi.org/10.1007/s10517-008-0233-0.

    Article  CAS  PubMed  Google Scholar 

  38. Postnikova, T. Y., Amakhin, D. V., Trofimova, A. M., Tumanova, N. L., Dubrovskaya, N. M., Kalinina, D. S., Kovalenko, A. A., Shcherbitskaia, A. D., Vasilev, D. S., and Zaitsev, A. V. (2022) Maternal hyperhomocysteinemia produces memory deficits associated with impairment of long-term synaptic plasticity in young rats, Cells, 12, 58, https://doi.org/10.3390/cells12010058.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Imbard, A., Benoist, J. F., and Blom, H. J. (2013) Neural tube defects, folic acid and methylation, Int. J. Environ. Res. Public Health, 10, 4352-4389, https://doi.org/10.3390/ijerph10094352.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Tang, K. F., Li, Y. L., and Wang, H. Y. (2015) Quantitative assessment of maternal biomarkers related to one-carbon metabolism and neural tube defects, Sci. Rep., 5, 8510, https://doi.org/10.1038/srep08510.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Murphy, M. M., Fernandez-Ballart, J. D., Molloy, A. M., and Canals, J. (2017) Moderately elevated maternal homocysteine at preconception is inversely associated with cognitive performance in children 4 months and 6 years after birth, Matern. Child Nutr., 13, e12289, https://doi.org/10.1111/mcn.12289.

    Article  PubMed  Google Scholar 

  42. Campoy, C., Azaryah, H., Torres-Espinola, F. J., Martinez-Zaldivar, C., Garcia-Santos, J. A., Demmelmair, H., Haile, G., Gyorei, E., Ramirez-Tortosa, M. D. C., Reischl, E., Rzehak, P., Molloy, A. M., Decsi, T., Luna, J. D., Koletzko, B., and Perez-Garcia, M. (2020) Long-chain polyunsaturated fatty acids, homocysteine at birth and fatty acid desaturase gene cluster polymorphisms are associated with Children’s processing speed up to age 9 years, Nutrients, 13, 131, https://doi.org/10.3390/nu13010131.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Srinivasan, K., Thomas, T., Kapanee, A. R., Ramthal, A., Bellinger, D. C., Bosch, R. J., Kurpad, A. V., and Duggan, C. (2017) Effects of maternal vitamin B12 supplementation on early infant neurocognitive outcomes: a randomized controlled clinical trial, Matern. Child Nutr., 13, e12325, https://doi.org/10.1111/mcn.12325.

    Article  PubMed  Google Scholar 

  44. Ars, C. L., Nijs, I. M., Marroun, H. E., Muetzel, R., Schmidt, M., Steenweg-de Graaff, J., van der Lugt, A., Jaddoe, V. W., Hofman, A., Steegers, E. A., Verhulst, F. C., Tiemeier, H., and White, T. (2019) Prenatal folate, homocysteine and vitamin B12 levels and child brain volumes, cognitive development and psychological functioning: the generation R study, Br. J. Nutr., 122, S1-S9, https://doi.org/10.1017/S0007114515002081.

    Article  CAS  PubMed  Google Scholar 

  45. Boldyrev, A. A. (2009) Molecular mechanisms of homocysteine toxicity, Biochemistry (Moscow), 74, 589-598, https://doi.org/10.1134/s0006297909060017.

    Article  CAS  PubMed  Google Scholar 

  46. Troen, A. M. (2005) The central nervous system in animal models of hyperhomocysteinemia, Prog. Neuropsychopharmacol. Biol. Psychiatry, 29, 1140-1151, https://doi.org/10.1016/j.pnpbp.2005.06.025.

    Article  CAS  PubMed  Google Scholar 

  47. Esse, R., Barroso, M., Tavares de Almeida, I., and Castro, R. (2019) The contribution of homocysteine metabolism disruption to endothelial dysfunction: state-of-the-art, Int. J. Mol. Sci., 20, 867, https://doi.org/10.3390/ijms20040867.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Faverzani, J. L., Hammerschmidt, T. G., Sitta, A., Deon, M., Wajner, M., and Vargas, C. R. (2017) Oxidative stress in homocystinuria due to cystathionine ss-synthase deficiency: findings in patients and in animal models, Cell. Mol. Neurobiol., 37, 1477-1485, https://doi.org/10.1007/s10571-017-0478-0.

    Article  CAS  PubMed  Google Scholar 

  49. Lehotsky, J., Tothova, B., Kovalska, M., Dobrota, D., Benova, A., Kalenska, D., and Kaplan, P. (2016) Role of homocysteine in the ischemic stroke and development of ischemic tolerance, Front. Neurosci., 10, 538, https://doi.org/10.3389/fnins.2016.00538.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Sibarov, D. A., Abushik, P. A., Giniatullin, R., and Antonov, S. M. (2016) GluN2A subunit-containing NMDA receptors are the preferential neuronal targets of homocysteine, Front. Cell. Neurosci., 10, 246, https://doi.org/10.3389/fncel.2016.00246.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Poddar, R. (2021) Hyperhomocysteinemia is an emerging comorbidity in ischemic stroke, Exp. Neurol., 336, 113541, https://doi.org/10.1016/j.expneurol.2020.113541.

    Article  CAS  PubMed  Google Scholar 

  52. Sharma, G. S., Kumar, T., Dar, T. A., and Singh, L. R. (2015) Protein N-homocysteinylation: From cellular toxicity to neurodegeneration, Biochim. Biophys. Acta, 1850, 2239-2245, https://doi.org/10.1016/j.bbagen.2015.08.013.

    Article  CAS  PubMed  Google Scholar 

  53. Jakubowski, H. (2019) Homocysteine modification in protein structure/function and human disease, Physiol. Rev., 99, 555-604, https://doi.org/10.1152/physrev.00003.2018.

    Article  CAS  PubMed  Google Scholar 

  54. Selhub, J. (1999) Homocysteine metabolism, Annu. Rev. Nutr., 19, 217-246, https://doi.org/10.1146/annurev.nutr.19.1.217.

    Article  CAS  PubMed  Google Scholar 

  55. Gueant, J. L., Namour, F., Gueant-Rodriguez, R. M., and Daval, J. L. (2013) Folate and fetal programming: a play in epigenomics?, Trends Endocrinol. Metab., 24, 279-289, https://doi.org/10.1016/j.tem.2013.01.010.

    Article  CAS  PubMed  Google Scholar 

  56. James, S. J., Melnyk, S., Pogribna, M., Pogribny, I. P., and Caudill, M. A. (2002) Elevation in S-adenosylhomocysteine and DNA hypomethylation: potential epigenetic mechanism for homocysteine-related pathology, J. Nutr., 132, 2361S-2366S, https://doi.org/10.1093/jn/132.8.2361S.

    Article  CAS  PubMed  Google Scholar 

  57. Hannibal, L., and Blom, H. J. (2017) Homocysteine and disease: causal associations or epiphenomenons?, Mol. Aspects Med., 53, 36-42, https://doi.org/10.1016/j.mam.2016.11.003.

    Article  CAS  PubMed  Google Scholar 

  58. Dayal, S., and Lentz, S. R. (2008) Murine models of hyperhomocysteinemia and their vascular phenotypes, Arterioscler. Thromb. Vasc. Biol., 28, 1596-1605, https://doi.org/10.1161/ATVBAHA.108.166421.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. McGee, M., Bainbridge, S., and Fontaine-Bisson, B. (2018) A crucial role for maternal dietary methyl donor intake in epigenetic programming and fetal growth outcomes, Nutr. Rev., 76, 469-478, https://doi.org/10.1093/nutrit/nuy006.

    Article  PubMed  Google Scholar 

  60. Heil, S. G., Herzog, E. M., Griffioen, P. H., van Zelst, B., Willemsen, S. P., de Rijke, Y. B., Steegers-Theunissen, R. P. M., and Steegers, E. A. P. (2019) Lower S-adenosylmethionine levels and DNA hypomethylation of placental growth factor (PlGF) in placental tissue of early-onset preeclampsia-complicated pregnancies, PLoS One, 14, e0226969, https://doi.org/10.1371/journal.pone.0226969.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Lin, N., Qin, S., Luo, S., Cui, S., Huang, G., and Zhang, X. (2014) Homocysteine induces cytotoxicity and proliferation inhibition in neural stem cells via DNA methylation in vitro, FEBS J., 281, 2088-2096, https://doi.org/10.1111/febs.12764.

    Article  CAS  PubMed  Google Scholar 

  62. Perla-Kajan, J., and Jakubowski, H. (2019) Dysregulation of epigenetic mechanisms of gene expression in the pathologies of hyperhomocysteinemia, Int. J. Mol. Sci., 20, 3140, https://doi.org/10.3390/ijms20133140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Kim, K. C., Friso, S., and Choi, S. W. (2009) DNA methylation, an epigenetic mechanism connecting folate to healthy embryonic development and aging, J. Nutr. Biochem., 20, 917-926, https://doi.org/10.1016/j.jnutbio.2009.06.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Bhutani, N., Burns, D. M., and Blau, H. M. (2011) DNA demethylation dynamics, Cell, 146, 866-872, https://doi.org/10.1016/j.cell.2011.08.042.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Freitag, M., and Selker, E. U. (2005) Controlling DNA methylation: many roads to one modification, Curr. Opin. Genet. Dev., 15, 191-199, https://doi.org/10.1016/j.gde.2005.02.003.

    Article  CAS  PubMed  Google Scholar 

  66. Weber, M., Hellmann, I., Stadler, M. B., Ramos, L., Paabo, S., Rebhan, M., and Schubeler, D. (2007) Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome, Nat. Genet., 39, 457-466, https://doi.org/10.1038/ng1990.

    Article  CAS  PubMed  Google Scholar 

  67. Jaenisch, R., and Bird, A. (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals, Nat. Genet., 33 Suppl., 245-254, https://doi.org/10.1038/ng1089.

    Article  CAS  PubMed  Google Scholar 

  68. Mandaviya, P. R., Stolk, L., and Heil, S. G. (2014) Homocysteine and DNA methylation: a review of animal and human literature, Mol. Genet. Metab., 113, 243-252, https://doi.org/10.1016/j.ymgme.2014.10.006.

    Article  CAS  PubMed  Google Scholar 

  69. Ito, S., D’Alessio, A. C., Taranova, O. V., Hong, K., Sowers, L. C., and Zhang, Y. (2010) Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification, Nature, 466, 1129-1133, https://doi.org/10.1038/nature09303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Tahiliani, M., Koh, K. P., Shen, Y., Pastor, W. A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L.M., Liu, D. R., Aravind, L., and Rao, A. (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1, Science, 324, 930-935, https://doi.org/10.1126/science.1170116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Globisch, D., Munzel, M., Muller, M., Michalakis, S., Wagner, M., Koch, S., Bruckl, T., Biel, M., and Carell, T. (2010) Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates, PLoS One, 5, e15367, https://doi.org/10.1371/journal.pone.0015367.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Song, C. X., Szulwach, K. E., Fu, Y., Dai, Q., Yi, C., Li, X., Li, Y., Chen, C. H., Zhang, W., Jian, X., Wang, J., Zhang, L., Looney, T. J., Zhang, B., Godley, L. A., Hicks, L. M., Lahn, B. T., Jin, P., and He, C. (2011) Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine, Nat. Biotechnol., 29, 68-72, https://doi.org/10.1038/nbt.1732.

    Article  CAS  PubMed  Google Scholar 

  73. Szulwach, K. E., Li, X., Li, Y., Song, C. X., Wu, H., Dai, Q., Irier, H., Upadhyay, A. K., Gearing, M., Levey, A. I., Vasanthakumar, A., Godley, L. A., Chang, Q., Cheng, X., He, C., and Jin, P. (2011) 5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging, Nat. Neurosci., 14, 1607-1616, https://doi.org/10.1038/nn.2959.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Scott, J. M., Molloy, A. M., Kennedy, D. G., Kennedy, S., and Weir, D. G. (1994) Effects of the disruption of transmethylation in the central nervous system: an animal model, Acta Neurol. Scand. Suppl., 154, 27-31, https://doi.org/10.1111/j.1600-0404.1994.tb05406.x.

    Article  CAS  PubMed  Google Scholar 

  75. Schatz, R. A., Wilens, T. E., and Sellinger, O. Z. (1981) Decreased transmethylation of biogenic amines after in vivo elevation of brain S-adenosyl-l-homocysteine, J. Neurochem., 36, 1739-1748, https://doi.org/10.1111/j.1471-4159.1981.tb00426.x.

    Article  CAS  PubMed  Google Scholar 

  76. Esse, R., Imbard, A., Florindo, C., Gupta, S., Quinlivan, E.P., Davids, M., Teerlink, T., Tavares de Almeida, I., Kruger, W. D., Blom, H. J., and Castro, R. (2014) Protein arginine hypomethylation in a mouse model of cystathionine beta-synthase deficiency, FASEB J., 28, 2686-2695, https://doi.org/10.1096/fj.13-246579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Lee, H. O., Wang, L., Kuo, Y. M., Gupta, S., Slifker, M. J., Li, Y. S., Andrews, A. J., and Kruger, W. D. (2017) Lack of global epigenetic methylation defects in CBS deficient mice, J. Inherit. Metab. Dis., 40, 113-120, https://doi.org/10.1007/s10545-016-9958-5.

    Article  CAS  PubMed  Google Scholar 

  78. DiBello, P. M., Dayal, S., Kaveti, S., Zhang, D., Kinter, M., Lentz, S. R., and Jacobsen, D. W. (2010) The nutrigenetics of hyperhomocysteinemia: quantitative proteomics reveals differences in the methionine cycle enzymes of gene-induced versus diet-induced hyperhomocysteinemia, Mol. Cell. Proteomics, 9, 471-485, https://doi.org/10.1074/mcp.M900406-MCP200.

    Article  CAS  PubMed  Google Scholar 

  79. Suszynska-Zajczyk, J., and Jakubowski, H. (2014) Paraoxonase 1 and dietary hyperhomocysteinemia modulate the expression of mouse proteins involved in liver homeostasis, Acta Biochim. Pol., 61, 815-823.

    Article  PubMed  Google Scholar 

  80. Li, J. G., Barrero, C., Gupta, S., Kruger, W. D., Merali, S., and Pratico, D. (2017) Homocysteine modulates 5-lipoxygenase expression level via DNA methylation, Aging Cell, 16, 273-280, https://doi.org/10.1111/acel.12550.

    Article  CAS  PubMed  Google Scholar 

  81. Pogribny, I. P., Karpf, A. R., James, S. R., Melnyk, S., Han, T., and Tryndyak, V. P. (2008) Epigenetic alterations in the brains of Fisher 344 rats induced by long-term administration of folate/methyl-deficient diet, Brain Res., 1237, 25-34, https://doi.org/10.1016/j.brainres.2008.07.077.

    Article  CAS  PubMed  Google Scholar 

  82. Kalani, A., Kamat, P. K., Familtseva, A., Chaturvedi, P., Muradashvili, N., Narayanan, N., Tyagi, S. C., and Tyagi, N. (2014) Role of microRNA29b in blood-brain barrier dysfunction during hyperhomocysteinemia: an epigenetic mechanism, J. Cereb. Blood Flow Metab., 34, 1212-1222, https://doi.org/10.1038/jcbfm.2014.74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kalani, A., Kamat, P. K., Givvimani, S., Brown, K., Metreveli, N., Tyagi, S. C., and Tyagi, N. (2014) Nutri-epigenetics ameliorates blood-brain barrier damage and neurodegeneration in hyperhomocysteinemia: role of folic acid, J. Mol. Neurosci., 52, 202-215, https://doi.org/10.1007/s12031-013-0122-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Fan, G., Beard, C., Chen, R. Z., Csankovszki, G., Sun, Y., Siniaia, M., Biniszkiewicz, D., Bates, B., Lee, P. P., Kuhn, R., Trumpp, A., Poon, C., Wilson, C. B., and Jaenisch, R. (2001) DNA hypomethylation perturbs the function and survival of CNS neurons in postnatal animals, J. Neurosci., 21, 788-797, https://doi.org/10.1523/JNEUROSCI.21-03-00788.2001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Hutnick, L. K., Golshani, P., Namihira, M., Xue, Z., Matynia, A., Yang, X. W., Silva, A. J., Schweizer, F. E., and Fan, G. (2009) DNA hypomethylation restricted to the murine forebrain induces cortical degeneration and impairs postnatal neuronal maturation, Hum. Mol. Genet., 18, 2875-2888, https://doi.org/10.1093/hmg/ddp222.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Liu, H. Y., Liu, S. M., and Zhang, Y. Z. (2020) Maternal folic acid supplementation mediates offspring health via DNA methylation, Reprod. Sci., 27, 963-976, https://doi.org/10.1007/s43032-020-00161-2.

    Article  CAS  PubMed  Google Scholar 

  87. Li, W., Li, Z., Li, S., Wang, X., Wilson, J. X., and Huang, G. (2018) Periconceptional folic acid supplementation benefit to development of early sensory-motor function through increase DNA methylation in rat offspring, Nutrients, 10, 292, https://doi.org/10.3390/nu10030292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Wang, X., Li, Z., Zhu, Y., Yan, J., Liu, H., Huang, G., and Li, W. (2021) Maternal folic acid impacts DNA methylation profile in male rat offspring implicated in neurodevelopment and learning/memory abilities, Genes Nutr., 16, 1, https://doi.org/10.1186/s12263-020-00681-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Karpova, N. N. (2014) Role of BDNF epigenetics in activity-dependent neuronal plasticity, Neuropharmacology, 76 Pt C, 709-718, https://doi.org/10.1016/j.neuropharm.2013.04.002.

    Article  CAS  PubMed  Google Scholar 

  90. Irwin, R. E., Pentieva, K., Cassidy, T., Lees-Murdock, D. J., McLaughlin, M., Prasad, G., McNulty, H., and Walsh, C. P. (2016) The interplay between DNA methylation, folate and neurocognitive development, Epigenomics, 8, 863-879, https://doi.org/10.2217/epi-2016-0003.

    Article  CAS  PubMed  Google Scholar 

  91. Martinowich, K., Hattori, D., Wu, H., Fouse, S., He, F., Hu, Y., Fan, G., and Sun, Y. E. (2003) DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation, Science, 302, 890-893, https://doi.org/10.1126/science.1090842.

    Article  CAS  PubMed  Google Scholar 

  92. Chen, W. G., Chang, Q., Lin, Y., Meissner, A., West, A. E., Griffith, E. C., Jaenisch, R., and Greenberg, M. E. (2003) Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2, Science, 302, 885-889, https://doi.org/10.1126/science.1086446.

    Article  CAS  PubMed  Google Scholar 

  93. Feng, J., Fouse, S., and Fan, G. (2007) Epigenetic regulation of neural gene expression and neuronal function, Pediatr. Res., 61, 58R-63R, https://doi.org/10.1203/pdr.0b013e3180457635.

    Article  CAS  PubMed  Google Scholar 

  94. Dhobale, M. V., Pisal, H. R., Mehendale, S. S., and Joshi, S. R. (2013) Differential expression of human placental neurotrophic factors in preterm and term deliveries, Int. J. Dev. Neurosci., 31, 719-723, https://doi.org/10.1016/j.ijdevneu.2013.09.006.

    Article  CAS  PubMed  Google Scholar 

  95. Dhobale, M. (2017) Neurotrophic factors and maternal nutrition during pregnancy, Vitam. Horm., 104, 343-366, https://doi.org/10.1016/bs.vh.2016.10.011.

    Article  CAS  PubMed  Google Scholar 

  96. Geng, H., Chen, H., Wang, H., and Wang, L. (2021) The histone modifications of neuronal plasticity, Neural. Plast., 2021, 6690523, https://doi.org/10.1155/2021/6690523.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Parrish, R. R., Buckingham, S. C., Mascia, K. L., Johnson, J. J., Matyjasik, M. M., Lockhart, R. M., and Lubin, F. D. (2015) Methionine increases BDNF DNA methylation and improves memory in epilepsy, Ann. Clin. Transl. Neurol., 2, 401-416, https://doi.org/10.1002/acn3.183.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Xu, P., Pang, D., Zhou, J., Li, S., Chen, D., and Yu, B. (2021) Behavioral changes and brain epigenetic alterations induced by maternal deficiencies of B vitamins in a mouse model, Psychopharmacology (Berl), 238, 1213-1222, https://doi.org/10.1007/s00213-021-05766-2.

    Article  CAS  PubMed  Google Scholar 

  99. Yan, Z., Jiao, F., Yan, X., and Ou, H. (2017) Maternal chronic folate supplementation ameliorates behavior disorders induced by prenatal high-fat diet through methylation alteration of BDNF and Grin2b in offspring hippocampus, Mol. Nutr. Food Res., 61, 1700461, https://doi.org/10.1002/mnfr.201700461.

    Article  CAS  Google Scholar 

  100. Suganuma, T., and Workman, J. L. (2011) Signals and combinatorial functions of histone modifications, Annu. Rev. Biochem., 80, 473-499, https://doi.org/10.1146/annurev-biochem-061809-175347.

    Article  CAS  PubMed  Google Scholar 

  101. Hyun, K., Jeon, J., Park, K., and Kim, J. (2017) Writing, erasing and reading histone lysine methylations, Exp. Mol. Med., 49, e324, https://doi.org/10.1038/emm.2017.11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Collins, B. E., Greer, C. B., Coleman, B. C., and Sweatt, J. D. (2019) Histone H3 lysine K4 methylation and its role in learning and memory, Epigenetics Chromatin, 12, 7, https://doi.org/10.1186/s13072-018-0251-8.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Mentch, S. J., Mehrmohamadi, M., Huang, L., Liu, X., Gupta, D., Mattocks, D., Gomez Padilla, P., Ables, G., Bamman, M. M., Thalacker-Mercer, A. E., Nichenametla, S. N., and Locasale, J. W. (2015) Histone methylation dynamics and gene regulation occur through the sensing of one-carbon metabolism, Cell Metab., 22, 861-873, https://doi.org/10.1016/j.cmet.2015.08.024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Shen, W., Gao, C., Cueto, R., Liu, L., Fu, H., Shao, Y., Yang, W. Y., Fang, P., Choi, E. T., Wu, Q., Yang, X., and Wang, H. (2020) Homocysteine-methionine cycle is a metabolic sensor system controlling methylation-regulated pathological signaling, Redox Biol., 28, 101322, https://doi.org/10.1016/j.redox.2019.101322.

    Article  CAS  PubMed  Google Scholar 

  105. Nan, X., Ng, H. H., Johnson, C. A., Laherty, C. D., Turner, B. M., Eisenman, R. N., and Bird, A. (1998) Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex, Nature, 393, 386-389, https://doi.org/10.1038/30764.

    Article  CAS  PubMed  Google Scholar 

  106. Barnes, C. E., English, D. M., and Cowley, S. M. (2019) Acetylation & Co: an expanding repertoire of histone acylations regulates chromatin and transcription, Essays Biochem., 63, 97-107, https://doi.org/10.1042/EBC20180061.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Rothbart, S. B., and Strahl, B. D. (2014) Interpreting the language of histone and DNA modifications, Biochim. Biophys. Acta, 1839, 627-643, https://doi.org/10.1016/j.bbagrm.2014.03.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Gurda, D., Handschuh, L., Kotkowiak, W., and Jakubowski, H. (2015) Homocysteine thiolactone and N-homocysteinylated protein induce pro-atherogenic changes in gene expression in human vascular endothelial cells, Amino Acids, 47, 1319-1339, https://doi.org/10.1007/s00726-015-1956-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Chaturvedi, P., Kalani, A., Givvimani, S., Kamat, P. K., Familtseva, A., and Tyagi, S. C. (2014) Differential regulation of DNA methylation versus histone acetylation in cardiomyocytes during HHcy in vitro and in vivo: an epigenetic mechanism, Physiol. Genomics, 46, 245-255, https://doi.org/10.1152/physiolgenomics.00168.2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Tothova, B., Kovalska, M., Kalenska, D., Tomascova, A., and Lehotsky, J. (2018) Histone hyperacetylation as a response to global brain ischemia associated with hyperhomocysteinemia in rats, Int. J. Mol. Sci., 19, 3147, https://doi.org/10.3390/ijms19103147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Tremolizzo, L., Doueiri, M. S., Dong, E., Grayson, D. R., Davis, J., Pinna, G., Tueting, P., Rodriguez-Menendez, V., Costa, E., and Guidotti, A. (2005) Valproate corrects the schizophrenia-like epigenetic behavioral modifications induced by methionine in mice, Biol. Psychiatry, 57, 500-509, https://doi.org/10.1016/j.biopsych.2004.11.046.

    Article  CAS  PubMed  Google Scholar 

  112. Dong, E., Guidotti, A., Grayson, D. R., and Costa, E. (2007) Histone hyperacetylation induces demethylation of reelin and 67-kDa glutamic acid decarboxylase promoters, Proc. Natl. Acad. Sci. USA, 104, 4676-4681, https://doi.org/10.1073/pnas.0700529104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Ma, Q., and Zhang, L. (2015) Epigenetic programming of hypoxic-ischemic encephalopathy in response to fetal hypoxia, Prog. Neurobiol., 124, 28-48, https://doi.org/10.1016/j.pneurobio.2014.11.001.

    Article  CAS  PubMed  Google Scholar 

  114. Wellmann, S., Bettkober, M., Zelmer, A., Seeger, K., Faigle, M., Eltzschig, H. K., and Buhrer, C. (2008) Hypoxia upregulates the histone demethylase JMJD1A via HIF-1, Biochem. Biophys. Res. Commun., 372, 892-897, https://doi.org/10.1016/j.bbrc.2008.05.150.

    Article  CAS  PubMed  Google Scholar 

  115. MacLennan, N. K., James, S. J., Melnyk, S., Piroozi, A., Jernigan, S., Hsu, J. L., Janke, S. M., Pham, T. D., and Lane, R. H. (2004) Uteroplacental insufficiency alters DNA methylation, one-carbon metabolism, and histone acetylation in IUGR rats, Physiol. Genomics, 18, 43-50, https://doi.org/10.1152/physiolgenomics.00042.2004.

    Article  PubMed  Google Scholar 

  116. Won, S. B., Han, A., and Kwon, Y. H. (2017) Maternal consumption of low-isoflavone soy protein isolate alters hepatic gene expression and liver development in rat offspring, J. Nutr. Biochem., 42, 51-61, https://doi.org/10.1016/j.jnutbio.2016.12.013.

    Article  CAS  PubMed  Google Scholar 

  117. Durbagula, S., Korlimarla, A., Ravikumar, G., Valiya Parambath, S., Kaku, S. M., and Visweswariah, A. M. (2022) Prenatal epigenetic factors are predisposing for neurodevelopmental disorders – considering placenta as a model, Birth Defects Res., 114, 1324-1342, https://doi.org/10.1002/bdr2.2119.

    Article  CAS  PubMed  Google Scholar 

  118. Rosenfeld, C. S. (2021) The placenta-brain-axis, J. Neurosci. Res., 99, 271-283, https://doi.org/10.1002/jnr.24603.

    Article  CAS  PubMed  Google Scholar 

  119. Nelissen, E.C., van Montfoort, A.P., Dumoulin, J.C., and Evers, J.L. (2011) Epigenetics and the placenta, Hum. Reprod. Update, 17, 397-417, https://doi.org/10.1093/humupd/dmq052.

    Article  CAS  PubMed  Google Scholar 

  120. Deshpande, S.S., and Balasinor, N.H. (2018) Placental Defects: An Epigenetic Perspective, Reprod. Sci., 25, 1143-1160, https://doi.org/10.1177/1933719118766265.

    Article  CAS  PubMed  Google Scholar 

  121. D’Souza, S. W., and Glazier, J. D. (2022) Homocysteine metabolism in pregnancy and developmental impacts, Front. Cell Dev. Biol., 10, 802285, https://doi.org/10.3389/fcell.2022.802285.

    Article  PubMed  PubMed Central  Google Scholar 

  122. Geng, Y., Gao, R., Chen, X., Liu, X., Liao, X., Li, Y., Liu, S., Ding, Y., Wang, Y., and He, J. (2015) Folate deficiency impairs decidualization and alters methylation patterns of the genome in mice, Mol. Hum. Reprod., 21, 844-856, https://doi.org/10.1093/molehr/gav045.

    Article  CAS  PubMed  Google Scholar 

  123. Kim, J. M., Hong, K., Lee, J. H., Lee, S., and Chang, N. (2009) Effect of folate deficiency on placental DNA methylation in hyperhomocysteinemic rats, J. Nutr. Biochem., 20, 172-176, https://doi.org/10.1016/j.jnutbio.2008.01.010.

    Article  CAS  PubMed  Google Scholar 

  124. Park, B. H., Kim, Y. J., Park, J. S., Lee, H. Y., Ha, E. H., Min, J. W., and Park, H. S. (2005) Folate and homocysteine levels during pregnancy affect DNA methylation in human placenta, J. Prev. Med. Public Health, 38, 437-442.

    PubMed  Google Scholar 

  125. Kulkarni, A., Dangat, K., Kale, A., Sable, P., Chavan-Gautam, P., and Joshi, S. (2011) Effects of altered maternal folic acid, vitamin B12 and docosahexaenoic acid on placental global DNA methylation patterns in Wistar rats, PLoS One, 6, e17706, https://doi.org/10.1371/journal.pone.0017706.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Li, B., Chang, S., Liu, C., Zhang, M., Zhang, L., Liang, L., Li, R., Wang, X., Qin, C., Zhang, T., Niu, B., and Wang, L. (2019) Low maternal dietary folate alters retrotranspose by methylation regulation in intrauterine growth retardation (IUGR) fetuses in a mouse model, Med. Sci. Monit., 25, 3354-3365, https://doi.org/10.12659/MSM.914292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Dai, C., Fei, Y., Li, J., Shi, Y., and Yang, X. (2021) A novel review of homocysteine and pregnancy complications, Biomed. Res. Int., 2021, 6652231, https://doi.org/10.1155/2021/6652231.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Nomura, Y., Lambertini, L., Rialdi, A., Lee, M., Mystal, E. Y., Grabie, M., Manaster, I., Huynh, N., Finik, J., Davey, M., Davey, K., Ly, J., Stone, J., Loudon, H., Eglinton, G., Hurd, Y., Newcorn, J. H., and Chen, J. (2014) Global methylation in the placenta and umbilical cord blood from pregnancies with maternal gestational diabetes, preeclampsia, and obesity, Reprod. Sci., 21, 131-137, https://doi.org/10.1177/1933719113492206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Lecuyer, M., Laquerriere, A., Bekri, S., Lesueur, C., Ramdani, Y., Jegou, S., Uguen, A., Marcorelles, P., Marret, S., and Gonzalez, B. J. (2017) PLGF, a placental marker of fetal brain defects after in utero alcohol exposure, Acta Neuropathol. Commun., 5, 44, https://doi.org/10.1186/s40478-017-0444-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Rahat, B., Hamid, A., Bagga, R., and Kaur, J. (2022) Folic acid levels during pregnancy regulate trophoblast invasive behavior and the possible development of preeclampsia, Front. Nutr., 9, 847136, https://doi.org/10.3389/fnut.2022.847136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Meister, S., Hahn, L., Beyer, S., Paul, C., Mitter, S., Kuhn, C., von Schonfeldt, V., Corradini, S., Sudan, K., Schulz, C., Kolben, T. M., Mahner, S., Jeschke, U., and Kolben, T. (2021) Regulation of epigenetic modifications in the placenta during preeclampsia: PPARgamma influences H3K4me3 and H3K9ac in extravillous trophoblast cells, Int. J. Mol. Sci., 22, 12469, https://doi.org/10.3390/ijms222212469.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Sheng, W., Gu, Y., Chu, X., Morgan, J. A., Cooper, D. B., Lewis, D. F., McCathran, C. E., and Wang, Y. (2021) Upregulation of histone H3K9 methylation in fetal endothelial cells from preeclamptic pregnancies, J. Cell. Physiol., 236, 1866-1874, https://doi.org/10.1002/jcp.29970.

    Article  CAS  PubMed  Google Scholar 

  133. Morales-Prieto, D. M., Chaiwangyen, W., Ospina-Prieto, S., Schneider, U., Herrmann, J., Gruhn, B., and Markert, U. R. (2012) MicroRNA expression profiles of trophoblastic cells, Placenta, 33, 725-734, https://doi.org/10.1016/j.placenta.2012.05.009.

    Article  CAS  PubMed  Google Scholar 

  134. Xie, L., Mouillet, J. F., Chu, T., Parks, W. T., Sadovsky, E., Knofler, M., and Sadovsky, Y. (2014) C19MC microRNAs regulate the migration of human trophoblasts, Endocrinology, 155, 4975-4985, https://doi.org/10.1210/en.2014-1501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Liang, Y., Ridzon, D., Wong, L., and Chen, C. (2007) Characterization of microRNA expression profiles in normal human tissues, BMC Genomics, 8, 166, https://doi.org/10.1186/1471-2164-8-166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Gunel, T., Kamali, N., Hosseini, M. K., Gumusoglu, E., Benian, A., and Aydinli, K. (2020) Regulatory effect of miR-195 in the placental dysfunction of preeclampsia, J. Matern. Fetal Neonatal Med., 33, 901-908, https://doi.org/10.1080/14767058.2018.1508439.

    Article  CAS  PubMed  Google Scholar 

  137. Li, J., Du, J., Wang, Z., Wang, C., Bai, J., and Zhang, S. (2018) Expression of miR-376 in blood of pregnant women with preeclampsia and its effect on 25-hydroxyvitamin D, Exp. Ther. Med., 16, 1701-1706, https://doi.org/10.3892/etm.2018.6394.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Lv, Y., Lu, C., Ji, X., Miao, Z., Long, W., Ding, H., and Lv, M. (2019) Roles of microRNAs in preeclampsia, J. Cell. Physiol., 234, 1052-1061, https://doi.org/10.1002/jcp.27291.

    Article  CAS  PubMed  Google Scholar 

  139. Cai, M., Kolluru, G. K., and Ahmed, A. (2017) Small molecule, big prospects: microRNA in pregnancy and its complications, J. Pregnancy, 2017, 6972732, https://doi.org/10.1155/2017/6972732.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Chen, D. B., and Wang, W. (2013) Human placental microRNAs and preeclampsia, Biol. Reprod., 88, 130, https://doi.org/10.1095/biolreprod.113.107805.

    Article  PubMed  PubMed Central  Google Scholar 

  141. Fu, G., Brkic, J., Hayder, H., and Peng, C. (2013) MicroRNAs in human placental development and pregnancy complications, Int. J. Mol. Sci., 14, 5519-5544, https://doi.org/10.3390/ijms14035519.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Escudero, C. A., Herlitz, K., Troncoso, F., Acurio, J., Aguayo, C., Roberts, J. M., Truong, G., Duncombe, G., Rice, G., and Salomon, C. (2016) Role of extracellular vesicles and microRNAs on dysfunctional angiogenesis during preeclamptic pregnancies, Front. Physiol., 7, 98, https://doi.org/10.3389/fphys.2016.00098.

    Article  PubMed  PubMed Central  Google Scholar 

  143. Rudov, A., Balduini, W., Carloni, S., Perrone, S., Buonocore, G., and Albertini, M. C. (2014) Involvement of miRNAs in placental alterations mediated by oxidative stress, Oxid. Med. Cell. Longev., 2014, 103068, https://doi.org/10.1155/2014/103068.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Sonkar, R., Kay, M. K., and Choudhury, M. (2019) PFOS modulates interactive epigenetic regulation in first-trimester human trophoblast cell line HTR-8/SVneo, Chem. Res. Toxicol., 32, 2016-2027, https://doi.org/10.1021/acs.chemrestox.9b00198.

    Article  CAS  PubMed  Google Scholar 

  145. Gold, A. R., and Glanzman, D. L. (2021) The central importance of nuclear mechanisms in the storage of memory, Biochem. Biophys. Res. Commun., 564, 103-113, https://doi.org/10.1016/j.bbrc.2021.04.125.

    Article  CAS  PubMed  Google Scholar 

  146. Jobe, E. M., and Zhao, X. (2017) DNA methylation and adult neurogenesis, Brain Plast., 3, 5-26, https://doi.org/10.3233/BPL-160034.

    Article  PubMed  PubMed Central  Google Scholar 

  147. Graff, J., and Mansuy, I. M. (2008) Epigenetic codes in cognition and behaviour, Behav. Brain Res., 192, 70-87, https://doi.org/10.1016/j.bbr.2008.01.021.

    Article  CAS  PubMed  Google Scholar 

  148. Wood, M. A., Hawk, J. D., and Abel, T. (2006) Combinatorial chromatin modifications and memory storage: a code for memory?, Learn Mem., 13, 241-244, https://doi.org/10.1101/lm.278206.

    Article  CAS  PubMed  Google Scholar 

  149. Hwang, J. Y., Aromolaran, K. A., and Zukin, R. S. (2017) The emerging field of epigenetics in neurodegeneration and neuroprotection, Nat. Rev. Neurosci., 18, 347-361, https://doi.org/10.1038/nrn.2017.46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Duman, R. S., and Aghajanian, G. K. (2012) Synaptic dysfunction in depression: potential therapeutic targets, Science, 338, 68-72, https://doi.org/10.1126/science.1222939.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Uchida, S., Yamagata, H., Seki, T., and Watanabe, Y. (2018) Epigenetic mechanisms of major depression: targeting neuronal plasticity, Psychiatry Clin. Neurosci., 72, 212-227, https://doi.org/10.1111/pcn.12621.

    Article  PubMed  Google Scholar 

  152. Kubota, T., Miyake, K., Hariya, N., and Mochizuki, K. (2015) Understanding the epigenetics of neurodevelopmental disorders and DOHaD, J. Dev. Orig. Health Dis., 6, 96-104, https://doi.org/10.1017/S2040174415000057.

    Article  CAS  PubMed  Google Scholar 

  153. Matrisciano, F., Tueting, P., Dalal, I., Kadriu, B., Grayson, D. R., Davis, J. M., Nicoletti, F., and Guidotti, A. (2013) Epigenetic modifications of GABAergic interneurons are associated with the schizophrenia-like phenotype induced by prenatal stress in mice, Neuropharmacology, 68, 184-194, https://doi.org/10.1016/j.neuropharm.2012.04.013.

    Article  CAS  PubMed  Google Scholar 

  154. Weaver, I. C., Cervoni, N., Champagne, F. A., D’Alessio, A. C., Sharma, S., Seckl, J. R., Dymov, S., Szyf, M., and Meaney, M. J. (2004) Epigenetic programming by maternal behavior, Nat. Neurosci., 7, 847-854, https://doi.org/10.1038/nn1276.

    Article  CAS  PubMed  Google Scholar 

  155. Kubota, T. (2018) Preemptive epigenetic medicine based on fetal programming, Adv. Exp. Med. Biol., 1012, 85-95, https://doi.org/10.1007/978-981-10-5526-3_9.

    Article  CAS  PubMed  Google Scholar 

  156. Arutyunyan, A. V., Zaloznyaya, I. V., Kerkeshko, G. O., Milyutina, Y. P., and Korenevskii, A. V. (2017) Prenatal hyperhomocysteinemia impairs hypothalamic regulation of reproductive cycles in rat progeny, Bull. Exp. Biol. Med., 162, 738-740, https://doi.org/10.1007/S10517-017-3701-6.

    Article  CAS  PubMed  Google Scholar 

  157. Wang, X., Li, W., Li, Z., Ma, Y., Yan, J., Wilson, J. X., and Huang, G. (2019) Maternal folic acid supplementation during pregnancy promotes neurogenesis and synaptogenesis in neonatal rat offspring, Cereb. Cortex, 29, 3390-3397, https://doi.org/10.1093/cercor/bhy207.

    Article  PubMed  Google Scholar 

  158. Loureiro, S. O., Heimfarth, L., Pelaez Pde, L., Vanzin, C. S., Viana, L., Wyse, A. T., and Pessoa-Pureur, R. (2008) Homocysteine activates calcium-mediated cell signaling mechanisms targeting the cytoskeleton in rat hippocampus, Int. J. Dev. Neurosci., 26, 447-455, https://doi.org/10.1016/j.ijdevneu.2008.03.001.

    Article  CAS  PubMed  Google Scholar 

  159. Lockhart, B., Jones, C., Cuisinier, C., Villain, N., Peyroulan, D., and Lestage, P. (2000) Inhibition of L-homocysteic acid and buthionine sulphoximine-mediated neurotoxicity in rat embryonic neuronal cultures with alpha-lipoic acid enantiomers, Brain Res., 855, 292-297, https://doi.org/10.1016/s0006-8993(99)02372-0.

    Article  CAS  PubMed  Google Scholar 

  160. Alzoubi, K.H., Aburashed, Z.O., and Mayyas, F. (2020) Edaravone protects from memory impairment induced by chronic L-methionine administration, Naunyn Schmiedebergs Arch. Pharmacol., 393, 1221-1228, https://doi.org/10.1007/s00210-020-01827-z.

    Article  CAS  PubMed  Google Scholar 

  161. Milyutina, Yu. P., Arutjunyan, A. V., Pustygina, A. V., Shcherbitskaya, A. D., Zaloznyaya, I. V., and Zorina, I. I. (2014) Content of catecholamines in the adrenal gland of rat pups subjected to prenatal hyperhomocysteinemia, Ross. Physiol. Zhurn. im. I. M. Sechenova, 100, 360-369.

    CAS  Google Scholar 

  162. Algaidi, S. A., Christie, L. A., Jenkinson, A. M., Whalley, L., Riedel, G., and Platt, B. (2006) Long-term homocysteine exposure induces alterations in spatial learning, hippocampal signalling and synaptic plasticity, Exp. Neurol., 197, 8-21, https://doi.org/10.1016/j.expneurol.2005.07.003.

    Article  CAS  PubMed  Google Scholar 

  163. Christie, L. A., Riedel, G., Algaidi, S. A., Whalley, L. J., and Platt, B. (2005) Enhanced hippocampal long-term potentiation in rats after chronic exposure to homocysteine, Neurosci. Lett., 373, 119-124, https://doi.org/10.1016/j.neulet.2004.09.072.

    Article  CAS  PubMed  Google Scholar 

  164. Viggiano, A., Viggiano, E., Monda, M., Ingrosso, D., Perna, A. F., and De Luca, B. (2012) Methionine-enriched diet decreases hippocampal antioxidant defences and impairs spontaneous behaviour and long-term potentiation in rats, Brain Res., 1471, 66-74, https://doi.org/10.1016/j.brainres.2012.06.048.

    Article  CAS  PubMed  Google Scholar 

  165. Christie, L. A., Riedel, G., and Platt, B. (2009) Bi-directional alterations of LTP after acute homocysteine exposure, Behav. Brain Res., 205, 559-563, https://doi.org/10.1016/j.bbr.2009.07.010.

    Article  CAS  PubMed  Google Scholar 

  166. Chai, G. S., Jiang, X., Ni, Z. F., Ma, Z. W., Xie, A. J., Cheng, X. S., Wang, Q., Wang, J. Z., and Liu, G. P. (2013) Betaine attenuates Alzheimer-like pathological changes and memory deficits induced by homocysteine, J. Neurochem., 124, 388-396, https://doi.org/10.1111/jnc.12094.

    Article  CAS  PubMed  Google Scholar 

  167. Zeng, P., Shi, Y., Wang, X. M., Lin, L., Du, Y. J., Tang, N., Wang, Q., Fang, Y. Y., Wang, J. Z., Zhou, X. W., Lu, Y., and Tian, Q. (2019) Emodin rescued hyperhomocysteinemia-induced dementia and Alzheimer’s disease-like features in rats, Int. J. Neuropsychopharmacol., 22, 57-70, https://doi.org/10.1093/ijnp/pyy090.

    Article  CAS  PubMed  Google Scholar 

  168. Mahaman, Y. A. R., Huang, F., Wu, M., Wang, Y., Wei, Z., Bao, J., Salissou, M. T. M., Ke, D., Wang, Q., Liu, R., Wang, J. Z., Zhang, B., Chen, D., and Wang, X. (2018) Moringa Oleifera alleviates homocysteine-induced Alzheimer’s disease-like pathology and cognitive impairments, J. Alzheimers Dis., 63, 1141-1159, https://doi.org/10.3233/JAD-180091.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Salissou, M. T. M., Mahaman, Y. A. R., Zhu, F., Huang, F., Wang, Y., Xu, Z., Ke, D., Wang, Q., Liu, R., Wang, J. Z., Zhang, B., and Wang, X. (2018) Methanolic extract of Tamarix Gallica attenuates hyperhomocysteinemia induced AD-like pathology and cognitive impairments in rats, Aging (Albany NY), 10, 3229-3248, https://doi.org/10.18632/aging.101627.

    Article  CAS  PubMed  Google Scholar 

  170. Kamat, P. K., Kyles, P., Kalani, A., and Tyagi, N. (2016) Hydrogen sulfide ameliorates homocysteine-induced Alzheimer’s disease-like pathology, blood-brain barrier disruption, and synaptic disorder, Mol. Neurobiol., 53, 2451-2467, https://doi.org/10.1007/s12035-015-9212-4.

    Article  CAS  PubMed  Google Scholar 

  171. Li, J. G., Barrero, C., Merali, S., and Pratico, D. (2017) Genetic absence of ALOX5 protects from homocysteine-induced memory impairment, tau phosphorylation and synaptic pathology, Hum. Mol. Genet., 26, 1855-1862, https://doi.org/10.1093/hmg/ddx088.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Li, J. G., Barrero, C., Merali, S., and Pratico, D. (2017) Five lipoxygenase hypomethylation mediates the homocysteine effect on Alzheimer’s phenotype, Sci. Rep., 7, 46002, https://doi.org/10.1038/srep46002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Akchiche, N., Bossenmeyer-Pourie, C., Kerek, R., Martin, N., Pourie, G., Koziel, V., Helle, D., Alberto, J. M., Ortiou, S., Camadro, J. M., Leger, T., Gueant, J. L., and Daval, J. L. (2012) Homocysteinylation of neuronal proteins contributes to folate deficiency-associated alterations of differentiation, vesicular transport, and plasticity in hippocampal neuronal cells, FASEB J., 26, 3980-3992, https://doi.org/10.1096/fj.12-205757.

    Article  CAS  PubMed  Google Scholar 

  174. Sibarov, D. A., Giniatullin, R., and Antonov, S. M. (2018) High sensitivity of cerebellar neurons to homocysteine is determined by expression of GluN2C and GluN2D subunits of NMDA receptors, Biochem. Biophys. Res. Commun., 506, 648-652, https://doi.org/10.1016/j.bbrc.2018.10.140.

    Article  CAS  PubMed  Google Scholar 

  175. Choe, Y. M., Sohn, B. K., Choi, H. J., Byun, M. S., Seo, E. H., Han, J. Y., Kim, Y. K., Yoon, E. J., Lee, J. M., Park, J., Woo, J. I., and Lee, D. Y. (2014) Association of homocysteine with hippocampal volume independent of cerebral amyloid and vascular burden, Neurobiol. Aging, 35, 1519-1525, https://doi.org/10.1016/j.neurobiolaging.2014.01.013.

    Article  CAS  PubMed  Google Scholar 

  176. Duan, W., Ladenheim, B., Cutler, R. G., Kruman, I. I., Cadet, J. L., and Mattson, M. P. (2002) Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons in models of Parkinson’s disease, J. Neurochem., 80, 101-110, https://doi.org/10.1046/j.0022-3042.2001.00676.x.

    Article  CAS  PubMed  Google Scholar 

  177. Alachkar, A., Wang, L., Yoshimura, R., Hamzeh, A. R., Wang, Z., Sanathara, N., Lee, S. M., Xu, X., Abbott, G. W., and Civelli, O. (2018) Prenatal one-carbon metabolism dysregulation programs schizophrenia-like deficits, Mol. Psychiatry, 23, 282-294, https://doi.org/10.1038/mp.2017.164.

    Article  CAS  PubMed  Google Scholar 

  178. Zhuo, J. M., Wang, H., and Pratico, D. (2011) Is hyperhomocysteinemia an Alzheimer’s disease (AD) risk factor, an AD marker, or neither?, Trends Pharmacol. Sci., 32, 562-571, https://doi.org/10.1016/j.tips.2011.05.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Velazquez, R., Ferreira, E., Winslow, W., Dave, N., Piras, I. S., Naymik, M., Huentelman, M. J., Tran, A., Caccamo, A., and Oddo, S. (2020) Maternal choline supplementation ameliorates Alzheimer's disease pathology by reducing brain homocysteine levels across multiple generations, Mol. Psychiatry, 25, 2620-2629, https://doi.org/10.1038/s41380-018-0322-z.

    Article  CAS  PubMed  Google Scholar 

  180. Da Silva, V. C., Fernandes, L., Haseyama, E. J., Agamme, A. L., Guerra Shinohara, E. M., Muniz, M. T., and D’Almeida, V. (2014) Effect of vitamin B deprivation during pregnancy and lactation on homocysteine metabolism and related metabolites in brain and plasma of mice offspring, PLoS One, 9, e92683, https://doi.org/10.1371/journal.pone.0092683.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Gulyaeva, N. V. (2017) Molecular mechanisms of neuroplasticity: an expanding universe, Biochemistry (Moscow), 82, 237-242, https://doi.org/10.1134/S0006297917030014.

    Article  CAS  PubMed  Google Scholar 

  182. Balaban, P. M. and Gulyaeva, N. V. (2006) Common molecular mechanisms of neuroplasticity and neuropathology: an integrative approach, Ross. Physiol. Zhurn. im. I. M. Sechenova, 92, 145-151.

    CAS  Google Scholar 

  183. Bacon, E. R., and Brinton, R. D. (2021) Epigenetics of the developing and aging brain: Mechanisms that regulate onset and outcomes of brain reorganization, Neurosci. Biobehav. Rev., 125, 503-516, https://doi.org/10.1016/j.neubiorev.2021.02.040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Liu, X. S., and Jaenisch, R. (2019) Editing the epigenome to tackle brain disorders, Trends Neurosci., 42, 861-870, https://doi.org/10.1016/j.tins.2019.10.003.

    Article  CAS  PubMed  Google Scholar 

  185. Sheikhi, S., and Saboory, E. (2015) Neuroplasticity changes of rat brain by musical stimuli during fetal period, Cell J., 16, 448-455, https://doi.org/10.22074/cellj.2015.490.

    Article  PubMed  PubMed Central  Google Scholar 

  186. Gao, J., Cahill, C. M., Huang, X., Roffman, J. L., Lamon-Fava, S., Fava, M., Mischoulon, D., and Rogers, J. T. (2018) S-Adenosyl methionine and transmethylation pathways in neuropsychiatric diseases throughout life, Neurotherapeutics, 15, 156-175, https://doi.org/10.1007/s13311-017-0593-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Taylor Levine, M., Gao, J., Satyanarayanan, S. K., Berman, S., Rogers, J. T., and Mischoulon, D. (2020) S-adenosyl-l-methionine (SAMe), cannabidiol (CBD), and kratom in psychiatric disorders: clinical and mechanistic considerations, Brain Behav. Immun., 85, 152-161, https://doi.org/10.1016/j.bbi.2019.07.013.

    Article  CAS  PubMed  Google Scholar 

  188. Remington, R., Bechtel, C., Larsen, D., Samar, A., Doshanjh, L., Fishman, P., Luo, Y., Smyers, K., Page, R., Morrell, C., and Shea, T. B. (2015) A phase II randomized clinical trial of a nutritional formulation for cognition and mood in Alzheimer’s disease, J. Alzheimers Dis., 45, 395-405, https://doi.org/10.3233/JAD-142499.

    Article  CAS  PubMed  Google Scholar 

  189. Gupta, R., Ambasta, R. K., and Kumar, P. (2021) Histone deacetylase in neuropathology, Adv. Clin. Chem., 104, 151-231, https://doi.org/10.1016/bs.acc.2020.09.004.

    Article  CAS  PubMed  Google Scholar 

  190. Fontana, A., Cursaro, I., Carullo, G., Gemma, S., Butini, S., and Campiani, G. (2022) A therapeutic perspective of HDAC8 in different diseases: an overview of selective inhibitors, Int. J. Mol. Sci., 23, 10014, https://doi.org/10.3390/ijms231710014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Ricci, R., and Colasante, G. (2021) CRISPR/dCas9 as a therapeutic approach for neurodevelopmental disorders: innovations and limitations compared to traditional strategies, Dev. Neurosci., 43, 253-261, https://doi.org/10.1159/000515845.

    Article  CAS  PubMed  Google Scholar 

  192. Peter, C.J., Saito, A., Hasegawa, Y., Tanaka, Y., Nagpal, M., Perez, G., Alway, E., Espeso-Gil, S., Fayyad, T., Ratner, C., Dincer, A., Gupta, A., Devi, L., Pappas, J.G., Lalonde, F.M., Butman, J.A., Han, J.C., Akbarian, S., and Kamiya, A. (2019) In vivo epigenetic editing of Sema6a promoter reverses transcallosal dysconnectivity caused by C11orf46/Arl14ep risk gene, Nat. Commun., 10, 4112, https://doi.org/10.1038/s41467-019-12013-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Liu, X.S., Wu, H., Krzisch, M., Wu, X., Graef, J., Muffat, J., Hnisz, D., Li, C.H., Yuan, B., Xu, C., Li, Y., Vershkov, D., Cacace, A., Young, R.A., and Jaenisch, R. (2018) Rescue of fragile X syndrome neurons by DNA methylation editing of the FMR1 gene, Cell, 172, 979-992.e6, https://doi.org/10.1016/j.cell.2018.01.012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Monayo, S. M., and Liu, X. (2022) The prospective application of melatonin in treating epigenetic dysfunctional diseases, Front. Pharmacol., 13, 867500, https://doi.org/10.3389/fphar.2022.867500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Alghamdi, B. S. (2018) The neuroprotective role of melatonin in neurological disorders, J. Neurosci. Res., 96, 1136-1149, https://doi.org/10.1002/jnr.24220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Leung, J. W., Cheung, K. K., Ngai, S. P., Tsang, H. W., and Lau, B. W. (2020) Protective effects of melatonin on neurogenesis impairment in neurological disorders and its relevant molecular mechanisms, Int. J. Mol. Sci., 21, 5645, https://doi.org/10.3390/ijms21165645.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Figueiro-Silva, J., Antequera, D., Pascual, C., de la Fuente Revenga, M., Volt, H., Acuna-Castroviejo, D., Rodriguez-Franco, M. I., and Carro, E. (2018) The melatonin analog IQM316 may induce adult hippocampal neurogenesis and preserve recognition memories in mice, Cell Transplant., 27, 423-437, https://doi.org/10.1177/0963689717721217.

    Article  PubMed  PubMed Central  Google Scholar 

  198. Ghareghani, M., Sadeghi, H., Zibara, K., Danaei, N., Azari, H., and Ghanbari, A. (2017) Melatonin increases oligodendrocyte differentiation in cultured neural stem cells, Cell. Mol. Neurobiol., 37, 1319-1324, https://doi.org/10.1007/s10571-016-0450-4.

    Article  CAS  PubMed  Google Scholar 

  199. Li, X., Chen, X., Zhou, W., Ji, S., Li, X., Li, G., Liu, G., Wang, F., and Hao, A. (2017) Effect of melatonin on neuronal differentiation requires CBP/p300-mediated acetylation of histone H3 lysine 14, Neuroscience, 364, 45-59, https://doi.org/10.1016/j.neuroscience.2017.07.064.

    Article  CAS  PubMed  Google Scholar 

  200. Liu, Y., Zhang, Z., Lv, Q., Chen, X., Deng, W., Shi, K., and Pan, L. (2016) Effects and mechanisms of melatonin on the proliferation and neural differentiation of PC12 cells, Biochem. Biophys. Res. Commun., 478, 540-545, https://doi.org/10.1016/j.bbrc.2016.07.093.

    Article  CAS  PubMed  Google Scholar 

  201. Kong, X., Li, X., Cai, Z., Yang, N., Liu, Y., Shu, J., Pan, L., and Zuo, P. (2008) Melatonin regulates the viability and differentiation of rat midbrain neural stem cells, Cell. Mol. Neurobiol., 28, 569-579, https://doi.org/10.1007/s10571-007-9212-7.

    Article  CAS  PubMed  Google Scholar 

  202. Paul, R., and Borah, A. (2015) The potential physiological crosstalk and interrelationship between two sovereign endogenous amines, melatonin and homocysteine, Life Sci., 139, 97-107, https://doi.org/10.1016/j.lfs.2015.07.031.

    Article  CAS  PubMed  Google Scholar 

  203. Karolczak, K., and Watala, C. (2021) Melatonin as a reducer of neuro- and vasculotoxic oxidative stress induced by homocysteine, Antioxidants (Basel), 10, 1178, https://doi.org/10.3390/antiox10081178.

    Article  CAS  PubMed  Google Scholar 

  204. Liu, J., Mesfin, F. M., Hunter, C. E., Olson, K. R., Shelley, W. C., Brokaw, J. P., Manohar, K., and Markel, T. A. (2022) Recent development of the molecular and cellular mechanisms of hydrogen sulfide gasotransmitter, Antioxidants (Basel), 11, 1788, https://doi.org/10.3390/antiox11091788.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This study was supported by the Russian Science Foundation (project no. 22-15-00393).

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Authors and Affiliations

  1. Ott Research Institute of Obstetrics, Gynecology and Reproductive Medicine, 199034, St. Petersburg, Russia

    Alexander V. Arutjunyan, Yulia P. Milyutina, Anastasia D. Shcherbitskaia, Gleb O. Kerkeshko & Irina V. Zalozniaia

  2. St. Petersburg Institute of Bioregulation and Gerontology, 197110, St. Petersburg, Russia

    Alexander V. Arutjunyan & Gleb O. Kerkeshko

  3. St. Petersburg State Pediatric Medical University, 194100, St. Petersburg, Russia

    Yulia P. Milyutina

  4. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223, St. Petersburg, Russia

    Anastasia D. Shcherbitskaia

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  1. Alexander V. Arutjunyan
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  4. Gleb O. Kerkeshko
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Contributions

A. V. Arutjunyan developed the review concept; A. V. Arutjunyan, G. O. Kerkeshko, Yu. P. Milyutina, A. D. Shcherbitskaia, and I. V. Zalozniaia collected and discussed the published data; A. V. Arutjunyan, G. O. Kerkeshko, Yu. P. Milyutina, A. D. Shcherbitskaia, and I. V. Zalozniaia wrote the manuscript; A. V. Arutjunyan and G. O. Kerkeshko edited the text.

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Correspondence to Alexander V. Arutjunyan.

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The authors declare no conflict of interests. This review does not contain studies involving humans or animal subject performed by any of the authors.

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Arutjunyan, A.V., Milyutina, Y.P., Shcherbitskaia, A.D. et al. Epigenetic Mechanisms Involved in the Effects of Maternal Hyperhomocysteinemia on the Functional State of Placenta and Nervous System Plasticity in the Offspring. Biochemistry Moscow 88, 435–456 (2023). https://doi.org/10.1134/S0006297923040016

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