A Comparative Analysis of CSF and the Blood Levels of Monoamines As Neurohormones in Rats during Ontogenesis.

According to the literature, the cerebrospinal fluid (CSF) in the cerebral ventricles contains numerous neuron-derived physiologically active substances that can function as neurohormones and contribute to volume neurotransmission in the periventricular region of the brain. This study was aimed at carrying out a comparative analysis of CSF and the blood levels of monoamines in rats during ontogenesis as an indicator of age-related characteristics of monoamine transport to body fluids and their function as neurohormones in volume neurotransmission in the periventricular region of the brain. We have shown that CSF in the perinatal period and adulthood contains the most functionally significant monoamines: dopamine, noradrenaline, and serotonin. A comparison of the monoamine levels in the CSF and blood of animals of different age groups revealed that CSF contains monoamines of predominantly neuronal (cerebral) origin and almost no monoamines derived from the general circulation. We also established that monoamines are found in the CSF at physiologically active levels that allow them to act as neurohormones in both reversible volume neurotransmission in the adult brain and irreversible regulation of brain development in the perinatal period.

Cooperative Synthesis of Dopamine in Rat Mediobasal Hypothalamus as a Compensatory Mechanism in Hyperprolactinemia.

Dopamine (DA), synthesized in the mediobasal hypothalamus by dopaminergic neurons containing two enzymes of DA synthesis - tyrosine hydroxylase and decarboxylase of aromatic L-amino acids, or by monoenzymatic non-dopaminergic neurons containing one DA synthesis enzyme in cooperation, is known to have an inhibitory effect on prolactin secretion. Deterioration of this inhibitory control leads to an increase in prolactin concentration in the blood and to the development of hyperprolactinemia syndrome. In a rat model of hyperprolactinemia induced by administration of a neurotoxin causing degeneration of dopaminergic and noradrenergic neurons, the level of DA first decreases, leading to an increase in prolactin level (decompensation stage), while later both levels are restored to normal (compensation stage). However, the mechanism of such compensation is still not clear. The aim of the present study was to analyze whether the increase in cooperative synthesis of DA by monoenzymatic neurons during hyperprolactinemia is a manifestation of a compensatory mechanism representing a particular case of neuroplasticity. The level of cooperative synthesis in the hyperprolactinemia model and in the control was estimated as the level of synthesis of DA and L-dihydroxyphenylalanine (L-DOPA) - an intermediate product of DA synthesis, when L-DOPA transfer from neurons containing tyrosine hydroxylase into neurons containing aromatic L-amino acid decarboxylase is inhibited. The level of DA synthesis during the decompensation stage was not changed, while during the compensation stage it was lower than the control. Along with a reduction in DA level, during the compensation stage an increase in the extracellular L-DOPA level in the medium was detected. Thus, the compensation of DA deficiency after degeneration of dopaminergic neurons in the mediobasal hypothalamus is due to the increase in cooperative synthesis of DA by monoenzymatic neurons containing one of the complementary enzymes of the DA synthesis pathway.

Plasticity of Central and Peripheral Sources of Noradrenaline in Rats during Ontogenesis.

The morphogenesis of individual organs and the whole organism occurs under the control of intercellular chemical signals mainly during the perinatal period of ontogenesis in rodents. In this study, we tested our hypothesis that the biologically active concentration of noradrenaline (NA) in blood in perinatal ontogenesis of rats is maintained due to humoral interaction between its central and peripheral sources based on their plasticity. As one of the mechanisms of plasticity, we examined changes in the secretory activity (spontaneous and stimulated release of NA) of NA-producing organs under deficiency of its synthesis in the brain. The destruction of NA-ergic neurons was provoked by administration of a hybrid molecular complex - antibodies against dopamine-ß-hydroxylase associated with the cytotoxin saporin - into the lateral cerebral ventricles of neonatal rats. We found that 72 h after the inhibition of NA synthesis in the brain, its spontaneous release from hypothalamus increased, which was most likely due to a compensatory increase of NA secretion from surviving neurons and can be considered as one of the mechanisms of neuroplasticity aimed at the maintenance of its physiological concentration in peripheral blood. Noradrenaline secretion from peripheral sources (adrenal glands and the organ of Zuckerkandl) also showed a compensatory increase in this model. Thus, during the critical period of morphogenesis, the brain is integrated into the system of NA-producing organs and participates in their reciprocal humoral regulation as manifested in compensatory enhancement of NA secretion in each of the studied sources of NA under specific inhibition of NA production in the brain.