Neurosteroid hormone vitamin D: modern prospects

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Abstract

Vitamin D (calciferol) is a key vitamin, playing an important role in the regulation of the musculoskeletal, immune, cardiovascular and nervous systems. Vitamin D deficiency is a risk factor for multiple brain disorders. Data are also accumulating on the neuroprotective properties of vitamin D, its ability to improve neuronal function and reduce brain disorders. Here, we focus on the latest clinical and preclinical (rodents and zebrafish) data on the role of vitamin D as a neurosteroid hormone, its role in regulating the synthesis and functions of neurotransmitters and neurotrophic factors. A better understanding of the role of vitamin D in brain function may lead to new approaches to the treatment and prevention of vitamin D deficiency-related brain disorders.

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About the authors

A. S. Lebedev

Almazov National Medical Research Center, Ministry of Health; Sirius University of Science and Technology; St. Petersburg State University

Email: avkalueff@gmail.com

Neurobiology Department, Research Center for Genetics and Life Sciences, Institute of Translational Biomedicine

Russian Federation, St. Petersburg; Sirius Federal Territory; St. Petersburg

A. D. Shevlyakov

Sirius University of Science and Technology

Email: avkalueff@gmail.com

Neurobiology Department, Research Center for Genetics and Life Sciences

Russian Federation, Sirius Federal Territory

N. P. Ilyin

Almazov National Medical Research Center, Ministry of Health; St. Petersburg State University

Email: avkalueff@gmail.com

Institute of Translational Biomedicine

Russian Federation, St. Petersburg; St. Petersburg

D. S. Galstyan

Almazov National Medical Research Center, Ministry of Health; St. Petersburg State University

Email: avkalueff@gmail.com

Institute of Translational Biomedicine

Russian Federation, St. Petersburg; St. Petersburg

K. V. Apukhtin

Sirius University of Science and Technology

Email: avkalueff@gmail.com

Neurobiology Department, Research Center for Genetics and Life Sciences

Russian Federation, Sirius Federal Territory

N. I. Golushko

St. Petersburg State University

Email: avkalueff@gmail.com

Institute of Translational Biomedicine

Russian Federation, St. Petersburg

A. V. Kaluev

Almazov National Medical Research Center, Ministry of Health; Sirius University of Science and Technology; St. Petersburg State University

Author for correspondence.
Email: avkalueff@gmail.com

Neurobiology Department, Research Center for Genetics and Life Sciences, Institute of Translational Biomedicine

Russian Federation, St. Petersburg; Sirius Federal Territory; St. Petersburg

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2. Fig. 1. Scheme of synthesis and biological action of vitamin D. DBP is a vitamin D-binding protein. Vitamin D is metabolized by further hydroxylation followed by excretion from the body with bile [17].

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3. Fig. 2. Relevance of vitamin D research in the CNS (the growth of publications on vitamin D and the brain in the Pubmed database, www.Pubmed.gov, as of August 2024 is shown). On the left is the general conservation of the VDR genes of humans, primates, rodents, amphibians, and zebrafish (Danio rerio), analyzed by nucleotide sequences in CDS in FASTA format according to the Ensembl database (www.ensembl.org/index.html, August 2024) as a phylogenetic tree created in the MEGA 11 program. At the bottom are the groups of CNS diseases affected by hypovitaminosis D and vitamin D therapy (see also details in Table 1 and the text)

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4. Fig. 3. Action of vitamin D on its specific nuclear (VDR) and membrane (mVDR) receptors. The distribution of VDR in different tissues and regions of the human brain (according to the Human Protein Atlas, www.proteinatlas.org/ENSG00000111424-VDR/, August 2024) and in the mouse brain (according to the Allen Brain Atlas, www.mouse.brain-map.org/experiment/show/100144119, August 2024) is summarized at the bottom. RXR is a retinoid receptor (forms a heterodimer with VDR in the nucleus upon binding vitamin D).

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5. Fig. 4. Analysis of the molecular pathways of vitamin D action via its receptors (VDR) using the BioGRID (www.thebiogrid.org/, August 2024, left) and KEGG (www.genome.jp/kegg/, right; arrows indicate processes related to the CNS). Below are the predicted biological activities (Pa) of calcitriol using the PASS Online database (www.way2drug.com/passonline/, August 2024) with a high probability Pa > 0.7 (see text for details).

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