The Role of Brain-Derived Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor in Chronic Fetal Oxygen Deprivation

N A Shchelchkova; A A Kokaya; V F Bezhenar'; O V Rozhdestvenskaya; M A Mamedova; T A Mishchenko; E V Mitroshina; M V Vedunova

doi:10.17691/stm2020.12.1.03

The Role of Brain-Derived Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor in Chronic Fetal Oxygen Deprivation

Sovrem Tekhnologii Med. 2020;12(1):25-31. doi: 10.17691/stm2020.12.1.03.

Authors

N A Shchelchkova¹, A A Kokaya², V F Bezhenar'³, O V Rozhdestvenskaya⁴, M A Mamedova⁵, T A Mishchenko⁶, E V Mitroshina⁷, M V Vedunova⁸

Affiliations

¹ Associate Professor, Department of Neurotechnologies, Institute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, Nizhny Novgorod, 603950, Russia, Head of Molecular and Cellular Technologies Department, Institute of Fundamental Medicine, Privolzhsky Research Medical University, 10/1 Minin and Pozharsky Square, Nizhny Novgorod, 603005, Russia.
² Obstetrician-Gynecologist, Pavlov University, 6-8 L'va Tolstogo St., Saint Petersburg, 197022, Russia.
³ Professor, Head of the Department of Obstetrics, Gynecology and Reproductology, Pavlov University, 6-8 L'va Tolstogo St., Saint Petersburg, 197022, Russia.
⁴ Senior Laboratory Assistant, Department of Obstetrics, Gynecology and Reproductology, Pavlov University, 6-8 L'va Tolstogo St., Saint Petersburg, 197022, Russia.
⁵ Assistant, Department of Obstetrics, Gynecology and Reproductology, Pavlov University, 6-8 L'va Tolstogo St., Saint Petersburg, 197022, Russia.
⁶ Senior Researcher, Laboratory for Neuroprotection Methods Development, Center for Translational Technologies, National Research Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, Nizhny Novgorod, 603950, Russia, Senior Researcher, Molecular and Cellular Technologies Department, Institute of Fundamental Medicine, Privolzhsky Research Medical University, 10/1 Minin and Pozharsky Square, Nizhny Novgorod, 603005, Russia.
⁷ Associate Professor, Department of Neurotechnologies, Institute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, Nizhny Novgorod, 603950, Russia, Senior Researcher, Laboratory for Neuroprotection Methods Development, Center for Translational Technologies, National Research Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, Nizhny Novgorod, 603950, Russia, Senior Researcher, Molecular and Cellular Technologies Department, Institute of Fundamental Medicine, Privolzhsky Research Medical University, 10/1 Minin and Pozharsky Square, Nizhny Novgorod, 603005, Russia.
⁸ Leading Researcher, Institute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, Nizhny Novgorod, 603950, Russia, Director of Institute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, Nizhny Novgorod, 603950, Russia.

Abstract

The aim of the study was to define the role of brain-derived and glial cell line-derived neurotrophic factors (BDNF and GDNF) in realization of compensative and adaptive mechanisms of a neonatal organism to hypoxia.

Materials and methods: The experiments in vivo have been carried out on pregnant C57BL/6 mice (n=36). Chronic hypobaric hypoxia has been modeled in different pregnancy trimesters. On gestation days E19-20, concentration of BDNF and GDNF in the blood of the pregnant females was determined by enzyme immunoassay. Further, the number of neonatal mice, their weight and body length parameters have been assessed.Parturient mothers (n=88) and their newborn babies followed up at the Clinic of Obstetrics and Gynecology of Pavlov University took part in the clinical investigations. Concentration of BDNF, GDNF, neuron-specific enolase (NSE), and hypoxia-inducible factor (HIF-1β) in the fetal cord blood has been determined by ELISA. The obtained data were retrospectively compared with cardiotocography, dopplerometry, presence of meconium-stained amniotic fluid and the neonate state at birth, assessment according to the Apgar score, and the course of adaptation period.

Results: Chronic hypobaric hypoxia in pregnant mice in trimester I and II resulted in the significant decrease of BDNF and GDNF level, decrease in the number of embryos, and in significant changes in weight/height characteristics of the newborn pups.According to the clinical observations, an increased expression of the neurotrophic factors BDNF, GDNF provides protection to a neonate even if hypoxia factors are present and realized. A low content of BDNF and GDNF was observed in the group of infants with a high risk of developing unfavorable hypoxic damaging effects.

Conclusion: The protective role of BDNF and GDNF in the regulation of fetal homeostasis in chronic hypoxia has been established experimentally and clinically.

Keywords: BDNF; GDNF; neuron-specific enolase; HIF-1β; NSE; brain-derived neurotrophic factor; glial cell line-derived neurotrophic factor; hypoxia-inducible factor; prenatal hypoxia.