The Influence of Stress on the Expression of Brain-Derived Neurotrophic Factor (BDNF) and Its Precursor proBDNF in Mice
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RIMENTAL ARTICLES
The Influence of Stress on the Expression of Brain-Derived Neurotrophic Factor (BDNF) and Its Precursor proBDNF in Mice with Different Sensitivity of Serotonin 5-HT1A Receptors E. M. Kondaurovaa, T. V. Il’chibaevaa, D. V. Bazovkinaa, N. K. Popovaa, and V. S. Naumenkoa, 1 aInstitute
of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia Received July 22, 2019; revised October 1, 2019; accepted October 3, 2019
Abstract—Recently, it has become apparent that the interaction between the serotonin (5-HT) system and the brain-derived neurotrophic factor (BDNF) system plays an important role in the regulation of behavior, and in various physiological and neuroplasticity processes. Moreover, there is data indicating the involvement of the 5-HT1A receptor, a key regulator of the central serotonergic system, in the control of the BDNF system. Recently, we have created new recombinant mouse strains, B6.CBA-D13Mit76C (B6-M76C) and B6.CBAD13Mit76B (B6-M76B) in which 5-HT1A receptors have different sensitivity to chronic activation. In this paper, using these mice, we studied acute stress-induced changes in the levels of BDNF protein and its precursor proBDNF. It was shown that B6-M76C mice with reduced sensitivity of presynaptic 5-HT1A receptors differ from B6-M76B mice; B6-M76C mice have a lower level of proBDNF in the midbrain and hippocampus and an increased BDNF/proBDNF ratio in the hippocampus. Acute stress caused a decrease in the level of proBDNF in the midbrain of mice of the control B6-M76B line leading to a significant increase in the BDNF/proBDNF ratio, which reflects the intensity of “maturation” of BDNF. Thus, it was discovered that changes in the sensitivity of the key regulator of the central serotonergic system, 5-HT1A receptor, lead to significant changes in the response of the BDNF system to acute stress. It was also revealed that the function of the 5-HT1A receptor is associated with the pattern of basal expression of elements of the BDNF system, namely, the expression of the proBDNF precursor protein. In addition, the data suggest that the changes in the functional activity of the BDNF system caused by acute stress are associated primarily with neuroplasticity mechanisms that determine the emotional and behavioral response to emotional stress. Keywords: brain-derived neurotrophic factor, BDNF, proBDNF precursor protein, protein level, stress, 5HT1A receptors, recombinant mouse lines DOI: 10.1134/S1819712420030071
INTRODUCTION Recently, it has become apparent that the two leading systems of brain neuroplasticity, the serotonergic (5-HT) and the brain-derived neurotrophic factor (BDNF) systems, are closely related and their interaction is extremely important both for the functioning of both systems and for the regulation of various physiological processes [1, 2]. Both the brain 5-HT and BDNF systems are very complex. BDNF is produced in a cell from the preproBDNF precursor protein, which is cleaved to proBDNF in the Golgi apparatus [3]. Then proBDNF may u
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