Laboratory of Neural and Neuroendocrine Regulations, Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilov str., 119334, Moscow, Russia.
Brain Struct Funct. 2019 Dec;224(9):3059-3073. doi: 10.1007/s00429-019-01950-5. Epub 2019 Sep 6.
The development of individual organs and the whole organism is under the control by morphogenetic factors over the critical period of morphogenesis. This study was aimed to test our hypothesis that the developing brain operates as an endocrine organ during morphogenesis, in rats during the perinatal period (Ugrumov in Neuro Chem 35:837-850, 2010). Norepinephrine, which is a morphogenetic factor, was used as a marker of the endocrine activity of the developing brain, although it is also secreted by peripheral organs. In this study, it was first shown that the concentration of norepinephrine in the peripheral blood of neonatal rats is sufficient to ensure the morphogenetic effect on the peripheral organs and the brain itself. Using pharmacological suppression of norepinephrine production in the brain, but not in peripheral organs, it was shown that norepinephrine is delivered from the brain to the general circulation in neonatal rats, that is, during morphogenesis. In fact, even partial suppression of norepinephrine production in the brain of neonatal rats led to a significant decrease of norepinephrine concentration in plasma, suggesting that at this time the brain is an important source of circulating norepinephrine. Conversely, the suppression of the production of norepinephrine in the brain of prepubertal rats did not cause a change in its concentration in plasma, showing no secretion of brain-derived norepinephrine to the bloodstream after morphogenesis. The above data support our hypothesis that morphogenetic factors, including norepinephrine, are delivered from the developing brain to the bloodstream, which occurs only during the critical period of morphogenesis.
个体器官和整个生物体的发育是由形态发生因子在形态发生的关键期控制的。本研究旨在检验我们的假设，即在围产期（Ugrumov in Neuro Chem 35:837-850, 2010）大鼠发育中的大脑作为内分泌器官在形态发生过程中起作用。去甲肾上腺素是一种形态发生因子，被用作发育中大脑内分泌活动的标志物，尽管它也由外周器官分泌。在这项研究中，首先表明新生大鼠外周血中的去甲肾上腺素浓度足以保证对周围器官和大脑本身的形态发生作用。通过抑制大脑而不是外周器官中的去甲肾上腺素产生，表明去甲肾上腺素在新生大鼠中从大脑传递到全身循环，即在形态发生过程中。事实上，即使是对新生大鼠大脑中去甲肾上腺素产生的部分抑制，也会导致血浆中去甲肾上腺素浓度显著降低，这表明此时大脑是循环去甲肾上腺素的重要来源。相反，抑制青春期前大鼠大脑中去甲肾上腺素的产生不会导致其在血浆中的浓度发生变化，这表明形态发生后，大脑中没有分泌到血流中的去甲肾上腺素。上述数据支持我们的假设，即形态发生因子（包括去甲肾上腺素）从发育中的大脑传递到血流中，这仅发生在形态发生的关键期。
