The developing brain as an endocrine source of norepinephrine in the blood

Saifetyarova, Yu. Yu.; Melnikova, V. I.; Sapronova, A. Ya.; Volina, E. V.; Ugrumov, M. V.

doi:10.1134/s0012496614010116

Cited by 4 publications

(4 citation statements)

References 10 publications

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“…This role involves their vesicular secretion by the pre-synaptic cell and interaction with receptors on the post-synaptic cell. However, neurotransmitters are also released outside synapses in high concentrations prior to blood-brain barrier development 21 , 22 and as part of non-synaptic forms of intercellular communication in the mature brain 23 . Synaptic transmission requires the rapid clearance of the secreted or released neurotransmitter via uptake by neurons and astrocytes 24 .…”

Section: Neurotransmitter Toxicity and Its Implication In Neurodegenementioning

confidence: 99%

Why are neurotransmitters neurotoxic? An evolutionary perspective

2014

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In the CNS, minor changes in the concentration of neurotransmitters such as glutamate or dopamine can lead to neurodegenerative diseases. We present an evolutionary perspective on the function of neurotransmitter toxicity in the CNS. We hypothesize that neurotransmitters are selected because of their toxicity, which serves as a test of neuron quality and facilitates the selection of neuronal pathways. This perspective may offer additional explanations for the reduction of neurotransmitter concentration in the CNS with age, and suggest an additional role for the blood-brain barrier. It may also suggest a connection between the specific toxicity of the neurotransmitters released in a specific region of the CNS, and elucidate their role as chemicals that are optimal for testing the quality of cells in that region.

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Section: Neurotransmitter Toxicity and Its Implication In Neurodegenementioning

confidence: 99%

Why are neurotransmitters neurotoxic? An evolutionary perspective

2014

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“…We have earlier shown in in vitro experiments that dopamine, at the concentration at which it is present in the peripheral blood of neonatal rats, inhibits prolactin secretion by the pituitary gland [10, 14]. However, pituitary cells are under the constant tonic influence of DA under in vivo conditions, while in in vitro conditions, the pituitary cells are contained in a medium without DA for a long period of time, which, according to some scientists, can fundamentally change cell physiology [15].…”

Section: Discussionmentioning

confidence: 99%

“…In adult animals, DA transferred from the hypothalamus to the pituitary gland regulates the function of peripheral targets only through the portal circulation system, whereas, according to our hypothesis, DA, in the absence of BBB in neonatal animals, can be also transferred from all populations of neurons directly into the systemic circulation. We have earlier shown in in vitro experiments that dopamine, at the concentration at which it is present in the peripheral blood of neonatal rats, inhibits prolactin secretion by the pituitary gland [ 10 , 14 ]. However, pituitary cells are under the constant tonic influence of DA under in vivo conditions, while in in vitro conditions, the pituitary cells are contained in a medium without DA for a long period of time, which, according to some scientists, can fundamentally change cell physiology [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

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The Effect of Dopamine Secreted by the Brain into the Systemic Circulation on Prolactin Synthesis by the Pituitary gland in Ontogenesis

2016

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This research was aimed at studying the brain’s endocrine function in ontogenesis. It has been previously shown in our laboratory that the brain serves as the source of dopamine in the systemic circulation of rats prior to the formation of the blood-brain barrier. This paper provides direct evidence that dopamine secreted by the brain directly into the systemic circulation in this period of ontogenesis has an inhibitory effect on prolactin secretion by pituitary cells. These results provide the basis for a fundamentally new understanding of the brain’s role in the neuroendocrine regulation of the development and function of peripheral target organs and, particularly in this study, the pituitary gland.

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Modeling of chronic selective inhibition of noradrenaline synthesis in the brain of neonatal rats

Zubova

Бондаренко

Sapronova

et al. 2015

Dokl Biochem Biophys

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Ontogenetic development and functioning of an organism are regulated by intracellular chemical sig naling; the signal molecules are secreted by the neu roendocrine system and function as morphogenetic or transcription factors affecting target cells and organs via specific receptors. Among the great variety of chemical signals controlling the development of target organs and tissues, noradrenaline (NA), which is syn thesized mainly by brain neurons, peripheral sym pathoadrenal system, and extra adrenal chromaffine tissue, is one of the most efficient factors exhibiting a broad range of physiological effects [1,2].We have proposed a hypothesis that, before the for mation of the blood-brain barrier (BBB), the brain functions as an endocrine organ secreting physiologi cally active substances into the general circulation and thus has a direct endocrine effect on the develop ment and functioning of peripheral target organs and tissues [3].Evidence efficiently supporting this hypothesis was obtained in our previous study using serotonin, dopamine (DA), and gonadotropin releasing hor mone as markers of endocrine functions of the devel oping brain [4].The purpose of the present work was to obtain direct evidence in support of our hypothesis that the developing brain functions as an endocrine source secreting NA into the general circulation. In particu lar, our aim was to develop a model of chronic (irre versible) suppression of NA synthesis by brain neurons in ontogeny before the BBB formation and to evaluate the changes in NA levels in the brain, peripheral blood, and peripheral organs using this model.The study was performed in male Wistar rats ana lyzed on postnatal days 2, 3, and 6 (P2, P3, and P6). The day when animals were born was considered post natal day 1. Animals were kept in a vivarium under standard conditions with unlimited food and water supply.Long term (chronic) pharmacological inhibition of NA synthesis in rat brain was ensured by adminis tration of 6 hydroxydopamine (6 OHDA), a specific neurotoxin that causes degeneration of catecholamin ergic neurons. Via DA and NA membrane transport ers, 6 OHDA is transported into the target cells and induces uncoupling of the oxidative phosphorylation chain and oxidative stress in mitochondria, which results in cell death [5]. GBR 12909, which inhibits 6 OHDA reuptake by DA neurons and thus acts as a specific neuroprotector, was administered systemi cally 60 min prior to 6 OHDA injections to prevent the death of dopaminergic neurons (DA neurons) [6].The first series of experiments was performed with 60 animals. Rats were subcutaneously injected first with 40 mg/kg GBR 12909 dihydrochloride (Tokris Bioscience, Great Britain), and then, 60 min later, with 250 or 150 μg 6 OHDA in 25 μL of 0.9% NaCl solution containing 0.1% ascorbic acid. The control animals received 0.9% NaCl instead of 6 OHDA.The second series of experiments was performed with 20 animals. Rats from the experimental group (ten animals) were administered with 150 μg 6 OHDA in 2 μL of 0.1% ascorbic acid s...

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The developing brain as an endocrine source of norepinephrine in the blood

Cited by 4 publications

References 10 publications

Why are neurotransmitters neurotoxic? An evolutionary perspective

Why are neurotransmitters neurotoxic? An evolutionary perspective

The Effect of Dopamine Secreted by the Brain into the Systemic Circulation on Prolactin Synthesis by the Pituitary gland in Ontogenesis

Modeling of chronic selective inhibition of noradrenaline synthesis in the brain of neonatal rats

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