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

  • Aliia R. Murtazina
  • Yulia O. Nikishina
  • Nadezhda S. Bondarenko
  • Liliya K. Dil’mukhametova
  • Anna Ya. Sapronova
  • Michael V. UgrumovEmail author
Original Article
  • 42 Downloads

Abstract

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.

Keywords

General Circulation Developing brain Norepinephrine Morphogenesis Rat 

Abbreviations

DHBA

Dihydroxybenzylamine

DBH

Dopamine ß-hydroxylase

E

Embryonic day

HPLC-ED

High performance liquid chromatography with electrochemical detection

6-OHDA

6-Hydroxydopamine

ICH

Immunocytochemistry

NE

Norepinephrine

PBS

Phosphate buffer saline

P

Postnatal day

Notes

Authors contributions

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.

Funding

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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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Aliia R. Murtazina
    • 1
  • Yulia O. Nikishina
    • 1
  • Nadezhda S. Bondarenko
    • 1
  • Liliya K. Dil’mukhametova
    • 1
  • Anna Ya. Sapronova
    • 1
  • Michael V. Ugrumov
    • 1
    Email author
  1. 1.Laboratory of Neural and Neuroendocrine RegulationsInstitute of Developmental Biology, Russian Academy of SciencesMoscowRussia

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