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The Effect of Hyperhomocysteinemia on the Content of Neurotrophins in Brain Structures of Pregnant Rats

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Abstract—Maternal hyperhomocysteinemia (HHC) during pregnancy was shown to lead to disruption of fetal nervous system development and cause long-term consequences, including cognitive dysfunction, in postnatal life. Impairment of methylation processes and the development of oxidative stress (OS) are among the major mechanisms of neurotoxic effects of homocysteine and its metabolites. A change in the level of neurotrophins in the hippocampus is one of the established consequences of HHC in adults. This study presents the results of the effect of HHC on the content of neurotrophins in various brain structures (hippocampus, hypothalamus, cerebral cortex, cerebellum) of rats on the 20th day of pregnancy. The daily dynamics of homocysteine content in these brain structures after single methionine loading on 4th day of pregnancy was analyzed. Although there were no changes in the levels of the pro-forms of the nerve growth factor (NGF) and brain neurotrophic factor (BDNF), there was a decrease in the content of the mature form of BDNF and an increase in the level of DNA methyltransferase 1 (DNMT1) both in the cerebral cortex and in the hypothalamus. At the same time, an increased level of the products of oxidative modification of proteins was noted in the cortex. No significant changes in the studied parameters were found in the hippocampus, which indicates its resistance to the toxic effect of HHC during pregnancy. Thus, a pathologic effect of HHC is manifested in the cortex and hypothalamus, which can lead to the development of anxiety-depressive states and negatively affect the health of the pregnant female and, accordingly, the developing fetus.

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Funding

This study was supported by the State Assignment grant no. 1021062812133-0-3.2.2 and grant of the Russian Foundation for Basic Research, project no. 18-015-00099-a.

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Authors and Affiliations

  1. Ott Research Institute of Obstetrics, Gynecology, and Reproductology, St. Petersburg, Russia

    Yu. P. Milyutina, A. V. Arutjunyan, A. D. Shcherbitskaia & I. V. Zalozniaia

  2. St. Petersburg State Pediatric Medical University, Russian Ministry of Health, St. Petersburg, Russia

    Yu. P. Milyutina

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

    A. D. Shcherbitskaia

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  1. Yu. P. Milyutina
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Correspondence to Yu. P. Milyutina.

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Ethical approval. All procedures performed in studies involving animals complied with the ethical standards of the institution in which the studies were conducted and the approved legal acts of the Russian Federation and international organizations.

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Corresponding author; address: Mendeleevskaya liniya 3, St. Petersburg, 199034 Russia; e-mail: milyutina1010@mail.ru.

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Milyutina, Y.P., Arutjunyan, A.V., Shcherbitskaia, A.D. et al. The Effect of Hyperhomocysteinemia on the Content of Neurotrophins in Brain Structures of Pregnant Rats. Neurochem. J. 16, 239–248 (2022). https://doi.org/10.1134/S1819712422030060

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