Bondarenko N S, Dilmukhametova L K, Kurina A Yu, Murtazina A R, Sapronova A Ya, Sysoeva A P, Ugrumov M V
Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, 119334, Russia.
Biochemistry (Mosc). 2017 Mar;82(3):373-379. doi: 10.1134/S0006297917030166.
The morphogenesis of individual organs and the whole organism occurs under the control of intercellular chemical signals mainly during the perinatal period of ontogenesis in rodents. In this study, we tested our hypothesis that the biologically active concentration of noradrenaline (NA) in blood in perinatal ontogenesis of rats is maintained due to humoral interaction between its central and peripheral sources based on their plasticity. As one of the mechanisms of plasticity, we examined changes in the secretory activity (spontaneous and stimulated release of NA) of NA-producing organs under deficiency of its synthesis in the brain. The destruction of NA-ergic neurons was provoked by administration of a hybrid molecular complex - antibodies against dopamine-β-hydroxylase associated with the cytotoxin saporin - into the lateral cerebral ventricles of neonatal rats. We found that 72 h after the inhibition of NA synthesis in the brain, its spontaneous release from hypothalamus increased, which was most likely due to a compensatory increase of NA secretion from surviving neurons and can be considered as one of the mechanisms of neuroplasticity aimed at the maintenance of its physiological concentration in peripheral blood. Noradrenaline secretion from peripheral sources (adrenal glands and the organ of Zuckerkandl) also showed a compensatory increase in this model. Thus, during the critical period of morphogenesis, the brain is integrated into the system of NA-producing organs and participates in their reciprocal humoral regulation as manifested in compensatory enhancement of NA secretion in each of the studied sources of NA under specific inhibition of NA production in the brain.
在啮齿动物个体发育的围产期，单个器官和整个生物体的形态发生主要在细胞间化学信号的控制下进行。在本研究中，我们验证了一个假设：基于可塑性，大鼠围产期个体发育过程中血液中去甲肾上腺素（NA）的生物活性浓度是通过其中枢和外周来源之间的体液相互作用来维持的。作为可塑性的机制之一，我们研究了在大脑中NA合成不足的情况下，NA产生器官的分泌活性（NA的自发释放和刺激释放）的变化。通过向新生大鼠的侧脑室注射一种混合分子复合物——与细胞毒素皂草素结合的抗多巴胺-β-羟化酶抗体，引发NA能神经元的破坏。我们发现，在大脑中NA合成受到抑制72小时后，其从下丘脑的自发释放增加，这很可能是由于存活神经元的NA分泌代偿性增加，并且可以被视为神经可塑性的机制之一，旨在维持其在外周血液中的生理浓度。在这个模型中，外周来源（肾上腺和主动脉旁神经节）的去甲肾上腺素分泌也出现了代偿性增加。因此，在形态发生的关键时期，大脑融入了NA产生器官系统，并参与它们之间的相互体液调节，表现为在大脑中NA产生受到特异性抑制时，每个被研究的NA来源中NA分泌的代偿性增强。
