Abstract
The extensive information accumulated over the past few decades on the important role of cerebrospinal fluid in many physiological processes in norm and pathology allowed the authors of the paper to express a hypothesis that the brain has its own endocrine system, which is represented by (a) brain neurons secreting neurohormones into the ventricles, (b) cerebrospinal fluid, a body fluid that ensures the delivery of neurohormones to the brain target regions, and (c) neurons of the periventricular region of the brain, targets for neurohormones contained in the cerebrospinal fluid. According to this hypothesis, the functional significance of the endocrine system of the brain in ontogenesis moves from the regulation of the neuron and brain development in the perinatal period to participation in volume neurotransmission in adulthood. This study is aimed at testing this hypothesis. Thus, in neonatal (fifth day of life) and adult (30th day of life) rats, it was shown that substances contained in the cerebrospinal fluid are involved in the regulation of monoamine secretion by brain neurons into the cerebrospinal fluid. These data were obtained by perfusion of cerebral ventricles with artificial cerebrospinal fluid with an increased content of K+. However, stimulation of the secretion of monoamines was not found in all animals within each age group, which is explained by the individual and age-related characteristics of the cerebrospinal fluid-brain barrier permeability. Indeed, perfusion of brain slices in the incubation medium with an increased content of K+ (in the absence of a cerebrospinal fluid-brain barrier) invariably led to the stimulation of monoamine secretion in all animals in both age groups. The second proof of the validity of our hypothesis was the demonstration of the uptake of substances from the cerebrospinal fluid into monoaminergic neurons of the brain, which are considered as potential targets for the endocrine factors of the cerebrospinal fluid. Evidence of this was obtained with the introduction into the cerebral ventricles of 4-[4-(dimethylamino)styryl]-N-methylpyridinium iodide, which has a high affinity for monoamine transporters. After intraventricular administration, this marker was incorporated into neurons in the periventricular region of the brain. Thus, evidence has been obtained that the substances contained in the cerebrospinal fluid in neonatal and adult rats are involved in the regulation of the secretion of monoamines in the cerebral ventricles, and monoamines contained in the cerebrospinal fluid enter the brain and are captured by potential target neurons.
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ACKNOWLEDGMENTS
The work was carried out using the equipment of the Center for Collective Use of the Koltzov Institute of Developmental Biology, Russian Academy of Sciences.
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The study was financially supported by the Russian Science Foundation (grant no. 20-14-00325).
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M.V. Ugryumov participated in the formulation of the work, the analysis of the results, and the writing of the article; T.S. Pronina participated in the analysis of the results and the design of the article; L.K. Dilmukhametova, K.I. Chandran, and T.S. Pronina participated in conducting experiments in vitro on slices; A.R. Murtazina, N.S. Bondarenko, and K.I. Chandran participated in conducting experiments in vivo with ventricular perfusion, V.V. Bogdanov, K.I. Chandran, and T.S. Pronina participated in conducting experiments in vivo with microdialysis of the ventricles; V.E. Blokhin, A.R. Murtazina, and T.S. Pronina participated in conducting experiments in vivo with ASP+.
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Statement on the welfare of animals. The experiments were carried out in accordance with the requirements of the National Institutes of Health (NIH Guide for the Care and Use of Laboratory Animals) and the Bioethics Committee of Koltsov Institute of Developmental Biology (protocol no. 3 dated September 10, 2020, and minutes no. 44 dated December 24, 2020). No people were used in this study as research subjects.
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Murtazina, A.R., Pronina, T.S., Chandran, K.I. et al. Hypothesis on the Endocrine System of the Brain: Evidence for the Regulated Delivery of Neurohormones from the Brain to the Cerebrospinal Fluid and Vice Versa in Neonatal and Prepubertal Periods of Ontogenesis. Russ J Dev Biol 52, 414–421 (2021). https://doi.org/10.1134/S1062360421060096
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DOI: https://doi.org/10.1134/S1062360421060096