Developing brain as a source of circulating norepinephrine in rats during the critical period of morphogenesis
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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.
KeywordsGeneral Circulation Developing brain Norepinephrine Morphogenesis Rat
High performance liquid chromatography with electrochemical detection
Phosphate buffer saline
MVU created the concept and design of the study, interpreted the experimental data; ARM, YON, NSB, AYS performed experiments, analyzed and interpreted biochemical data; LKD carried out immunohistochemistry and image analysis, prepared figures. All authors have approved the final manuscript and agree to be accountable for all aspects of the work.
This research was supported by the Russian Science Foundation: Grants № 14-15-01122 and № 17-14-01422 for the study of the brain-blood barrier permeability in newborn and adult rats, respectively.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
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