Developing brain as a source of circulating norepinephrine in rats during the critical period of morphogenesis

• Published in: Brain Structure and Function Vol. 224; no. 9; pp. 3059 - 3073
• Main Authors: Murtazina, Aliia R., Nikishina, Yulia O., Bondarenko, Nadezhda S., Dil’mukhametova, Liliya K., Sapronova, Anna Ya, Ugrumov, Michael V.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2019; Springer Nature B.V
• Subjects: Animals; Antidepressants; Biomedical and Life Sciences; Biomedicine; Brain - growth & development; Catecholamines; Cell Biology; Critical period; Endocrine System - physiology; Female; Hypotheses; Male; Morphogenesis; Neonates; Neurology; Neurons - physiology; Neurosciences; Norepinephrine; Norepinephrine - blood; Norepinephrine - physiology; Original Article; Peripheral blood; Rats, Wistar; Secretion; Morphogenesis; Developing brain; General; Norepinephrine; Rat; Circulation
• ISSN: 1863-2653; 1863-2661; 0340-2061
• DOI: 10.1007/s00429-019-01950-5

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.