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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
Neurochemical Journal ( IF 0.5 ) Pub Date : 2020-09-23 , DOI: 10.1134/s1819712420030071
E. M. Kondaurova , T. V. Il’chibaeva , D. V. Bazovkina , N. K. Popova , V. S. Naumenko

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.CBA-D13Mit76B (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.



中文翻译:

应激对不同敏感性5-羟色胺5-HT1A受体的小鼠脑源性神经营养因子(BDNF)及其前体proBDNF表达的影响

摘要—最近,很明显,5-羟色胺(5-HT)系统与脑源性神经营养因子(BDNF)系统之间的相互作用在行为调节以及各种生理和神经可塑性过程中起着重要作用。而且,有数据表明5-HT 1A受体是中央5-羟色胺能系统的关键调节剂,参与了BDNF系统的控制。最近,我们创建了新的重组小鼠品系B6.CBA-D13Mit76C(B6-M76C)和B6.CBA-D13Mit76B(B6-M76B),其中5-HT 1A受体对慢性激活具有不同的敏感性。在本文中,我们使用这些小鼠研究了急性应激诱导的BDNF蛋白及其前体proBDNF水平的变化。结果表明,对突触前5-HT 1A受体敏感性降低的B6-M76C小鼠与B6-M76B小鼠不同。B6-M76C小鼠在中脑和海马中的proBDNF含量较低,在海马中的BDNF / proBDNF比值升高。急性应激导致对照B6-M76B系小鼠中脑中proBDNF水平降低,导致BDNF / proBDNF比值显着增加,这反映了BDNF“成熟”的强度。因此,发现中央5-羟色胺能系统关键调节剂5-HT 1A的敏感性发生了变化。受体,导致BDNF系统对急性应激反应的显着变化。还揭示了5-HT 1A受体的功能与BDNF系统元件的基础表达的模式,即proBDNF前体蛋白的表达有关。此外,数据表明由急性应激引起的BDNF系统功能活动的变化主要与神经可塑性机制有关,该机制决定了对情绪应激的情绪和行为反应。

更新日期:2020-09-25
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