Maternal Hyperhomocysteinemia Disturbs the Mechanisms of Embryonic Brain Development and Its Maturation in Early Postnatal Ontogenesis
Maternal hyperhomocysteinemia causes the disruption of placental blood flow and can lead to serious disturbances in the formation of the offspring’s brain. In the present study, the effects of prenatal hyperhomocysteinemia (PHHC) on the neuronal migration, neural tissue maturation, and the expressio...
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MDPI AG
2023-01-01
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| author | Dmitrii S. Vasilev Anastasiia D. Shcherbitskaia Natalia L. Tumanova Anastasiia V. Mikhel Yulia P. Milyutina Anna A. Kovalenko Nadezhda M. Dubrovskaya Daria B. Inozemtseva Irina V. Zalozniaia Alexander V. Arutjunyan |
| author_facet | Dmitrii S. Vasilev Anastasiia D. Shcherbitskaia Natalia L. Tumanova Anastasiia V. Mikhel Yulia P. Milyutina Anna A. Kovalenko Nadezhda M. Dubrovskaya Daria B. Inozemtseva Irina V. Zalozniaia Alexander V. Arutjunyan |
| author_sort | Dmitrii S. Vasilev |
| collection | DOAJ |
| description | Maternal hyperhomocysteinemia causes the disruption of placental blood flow and can lead to serious disturbances in the formation of the offspring’s brain. In the present study, the effects of prenatal hyperhomocysteinemia (PHHC) on the neuronal migration, neural tissue maturation, and the expression of signaling molecules in the rat fetal brain were described. Maternal hyperhomocysteinemia was induced in female rats by per os administration of 0.15% aqueous methionine solution in the period of days 4–21 of pregnancy. Behavioral tests revealed a delay in PHHC male pups maturing. Ultrastructure of both cortical and hippocampus tissue demonstrated the features of the developmental delay. PHHC was shown to disturb both generation and radial migration of neuroblasts into the cortical plate. Elevated <i>Bdnf</i> expression, together with changes in proBDNF/mBDNF balance, might affect neuronal cell viability, positioning, and maturation in PHHC pups. Reduced <i>Kdr</i> gene expression and the content of SEMA3E might lead to impaired brain development. In the brain tissue of E20 PHHC fetuses, the content of the procaspase-8 was decreased, and the activity level of the caspase-3 was increased; this may indicate the development of apoptosis. PHHC disturbs the mechanisms of early brain development leading to a delay in brain tissue maturation and formation of the motor reaction of pups. |
| first_indexed | 2024-03-11T10:04:43Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T10:04:43Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-32abdb7840b94e4ca60b5477ea359c8a2023-11-16T15:07:18ZengMDPI AGCells2073-44092023-01-0112118910.3390/cells12010189Maternal Hyperhomocysteinemia Disturbs the Mechanisms of Embryonic Brain Development and Its Maturation in Early Postnatal OntogenesisDmitrii S. Vasilev0Anastasiia D. Shcherbitskaia1Natalia L. Tumanova2Anastasiia V. Mikhel3Yulia P. Milyutina4Anna A. Kovalenko5Nadezhda M. Dubrovskaya6Daria B. Inozemtseva7Irina V. Zalozniaia8Alexander V. Arutjunyan9I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 194223 St. Petersburg, RussiaI. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 194223 St. Petersburg, RussiaI. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 194223 St. Petersburg, RussiaI. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 194223 St. Petersburg, RussiaD.O. Ott Research Institute of Obstetrics, Gynecology and Reproductive Medicine, 199034 St. Petersburg, RussiaI. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 194223 St. Petersburg, RussiaI. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 194223 St. Petersburg, RussiaD.O. Ott Research Institute of Obstetrics, Gynecology and Reproductive Medicine, 199034 St. Petersburg, RussiaD.O. Ott Research Institute of Obstetrics, Gynecology and Reproductive Medicine, 199034 St. Petersburg, RussiaD.O. Ott Research Institute of Obstetrics, Gynecology and Reproductive Medicine, 199034 St. Petersburg, RussiaMaternal hyperhomocysteinemia causes the disruption of placental blood flow and can lead to serious disturbances in the formation of the offspring’s brain. In the present study, the effects of prenatal hyperhomocysteinemia (PHHC) on the neuronal migration, neural tissue maturation, and the expression of signaling molecules in the rat fetal brain were described. Maternal hyperhomocysteinemia was induced in female rats by per os administration of 0.15% aqueous methionine solution in the period of days 4–21 of pregnancy. Behavioral tests revealed a delay in PHHC male pups maturing. Ultrastructure of both cortical and hippocampus tissue demonstrated the features of the developmental delay. PHHC was shown to disturb both generation and radial migration of neuroblasts into the cortical plate. Elevated <i>Bdnf</i> expression, together with changes in proBDNF/mBDNF balance, might affect neuronal cell viability, positioning, and maturation in PHHC pups. Reduced <i>Kdr</i> gene expression and the content of SEMA3E might lead to impaired brain development. In the brain tissue of E20 PHHC fetuses, the content of the procaspase-8 was decreased, and the activity level of the caspase-3 was increased; this may indicate the development of apoptosis. PHHC disturbs the mechanisms of early brain development leading to a delay in brain tissue maturation and formation of the motor reaction of pups.https://www.mdpi.com/2073-4409/12/1/189homocysteineelectron microscopyneurotrophinssemaphorincaspasematrix metalloproteinase |
| spellingShingle | Dmitrii S. Vasilev Anastasiia D. Shcherbitskaia Natalia L. Tumanova Anastasiia V. Mikhel Yulia P. Milyutina Anna A. Kovalenko Nadezhda M. Dubrovskaya Daria B. Inozemtseva Irina V. Zalozniaia Alexander V. Arutjunyan Maternal Hyperhomocysteinemia Disturbs the Mechanisms of Embryonic Brain Development and Its Maturation in Early Postnatal Ontogenesis Cells homocysteine electron microscopy neurotrophins semaphorin caspase matrix metalloproteinase |
| title | Maternal Hyperhomocysteinemia Disturbs the Mechanisms of Embryonic Brain Development and Its Maturation in Early Postnatal Ontogenesis |
| title_full | Maternal Hyperhomocysteinemia Disturbs the Mechanisms of Embryonic Brain Development and Its Maturation in Early Postnatal Ontogenesis |
| title_fullStr | Maternal Hyperhomocysteinemia Disturbs the Mechanisms of Embryonic Brain Development and Its Maturation in Early Postnatal Ontogenesis |
| title_full_unstemmed | Maternal Hyperhomocysteinemia Disturbs the Mechanisms of Embryonic Brain Development and Its Maturation in Early Postnatal Ontogenesis |
| title_short | Maternal Hyperhomocysteinemia Disturbs the Mechanisms of Embryonic Brain Development and Its Maturation in Early Postnatal Ontogenesis |
| title_sort | maternal hyperhomocysteinemia disturbs the mechanisms of embryonic brain development and its maturation in early postnatal ontogenesis |
| topic | homocysteine electron microscopy neurotrophins semaphorin caspase matrix metalloproteinase |
| url | https://www.mdpi.com/2073-4409/12/1/189 |
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