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New Research on Endocrine Regulation of Brain Development

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (20 September 2022) | Viewed by 9229

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Special Issue Editors

Prof. Dr. David W. Walker

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Guest Editor

School of Health & Biomedical Sciences, RMIT University, Melbourne, Australia
Interests: fetal and neonatal physiology; placental physiology; brain development; neuroendocrinology; development of sleep and behaviour; hypothalamic-pituitary axis; adrenal gland

Prof. Dr. Jonathan J. Hirst

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Guest Editor

School of Biomedical Sciences and Pharmacy, Mothers and Babies Research Centre, University of Newcas-tle, Callaghan, New South Wales, Australia
Interests: fetal development; premature birth; neurosteroids; progesterone; placental endocrinology; prenatal stress

Special Issue Information

Dear Colleagues,

This issue of the journal is dedicated to the discussion of the regulation of prenatal and postnatal development of the brain by endocrine factors, for which we invite contributions from researchers and clinicians of original research papers, review articles, or commentaries related to this topic. Highlights in the field of normal and abnormal brain development, and the role(s) of maternal, placental, and fetal endocrinology will be addressed.

The epidemiological and experimental evidence that stress, illness, or nutritional deprivation during pregnancy will impact on the structural and functional development of the brain is now compelling. This may cause not only catastrophic damage to the brain at birth, as shown by brain damage that leads to cerebral palsy, but also more subtle and long-term effects that manifest as behavioural disorders as the child develops, such as autism, schizophrenia, and compulsive/addictive behaviours, and in determining appetite and the physical and metabolic development of the individual. All of these processes are modulated by hormonal factors arising during pregnancy in the mother, but also in the placenta, and having effects on fetal endocrine systems, recognised clinically as the feto-placental axis. The impact of all these factors will be discussed by experts currently involved in research designed to identify the role of hormones in determining the trajectory of brain and behavioural development.

Prof. Dr. David W. Walker
Prof. Dr. Jonathan J. Hirst
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Neurosteroids
Preterm birth
Fetal brain
Perinatal brain injury
Early life and prenatal stress

Published Papers (3 papers)

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Research

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16 pages, 5104 KiB

Open AccessArticle

Folate and Cobalamin Deficiencies during Pregnancy Disrupt the Glucocorticoid Response in Hypothalamus through N-Homocysteinilation of the Glucocorticoid Receptor

by Arnaud Michel, Tunay Kokten, Lynda Saber-Cherif, Rémy Umoret, Jean-Marc Alberto, Déborah Helle, Amélia Julien, Jean-Luc Daval, Jean-Louis Guéant, Carine Bossenmeyer-Pourié and Grégory Pourié

Int. J. Mol. Sci. 2023, 24(12), 9847; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24129847 - 07 Jun 2023

Cited by 1 | Viewed by 1004

Abstract

Vitamin B9 (folate)/B12 (cobalamin) deficiency is known to induce brain structural and/or functional retardations. In many countries, folate supplementation, targeting the most severe outcomes such as neural tube defects, is discontinued after the first trimester. However, adverse effects may occur after birth because of some mild misregulations. Various hormonal receptors were shown to be deregulated in brain tissue under these conditions. The glucocorticoid receptor (GR) is particularly sensitive to epigenetic regulation and post-translational modifications. In a mother–offspring rat model of vitamin B9/B12 deficiency, we investigated whether a prolonged folate supplementation could restore the GR signaling in the hypothalamus. Our data showed that a deficiency of folate and vitamin B12 during the in-utero and early postnatal periods was associated with reduced GR expression in the hypothalamus. We also described for the first time a novel post-translational modification of GR that impaired ligand binding and GR activation, leading to decrease expression of one of the GR targets in the hypothalamus, AgRP. Moreover, this brain-impaired GR signaling pathway was associated with behavioral perturbations during offspring growth. Importantly, perinatal and postnatal supplementation with folic acid helped restore GR mRNA levels and activity in hypothalamus cells and improved behavioral deficits. Full article

(This article belongs to the Special Issue New Research on Endocrine Regulation of Brain Development)

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13 pages, 1129 KiB

Open AccessArticle

Exploring the Impact of the Microbiome on Neuroactive Steroid Levels in Germ-Free Animals

by Silvia Diviccaro, Valentina Caputi, Lucia Cioffi, Silvia Giatti, Joshua M. Lyte, Donatella Caruso, Siobhain M. O’Mahony and Roberto Cosimo Melcangi

Int. J. Mol. Sci. 2021, 22(22), 12551; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212551 - 21 Nov 2021

Cited by 13 | Viewed by 2035

Abstract

Steroid hormones are essential biomolecules for human physiology as they modulate the endocrine system, nervous function and behaviour. Recent studies have shown that the gut microbiota is directly involved in the production and metabolism of steroid hormones in the periphery. However, the influence of the gut microbiota on levels of steroids acting and present in the brain (i.e., neuroactive steroids) is not fully understood. Therefore, using liquid chromatography–tandem mass spectrometry, we assessed the levels of several neuroactive steroids in various brain areas and the plasma of germ-free (GF) male mice and conventionally colonized controls. The data obtained indicate an increase in allopregnanolone levels associated with a decrease in those of 5α-androstane-3α, 17β-diol (3α-diol) in the plasma of GF mice. Moreover, an increase of dihydroprogesterone and isoallopregnanolone in the hippocampus, cerebellum, and cerebral cortex was also reported. Changes in dihydrotestosterone and 3α-diol levels were also observed in the hippocampus of GF mice. In addition, an increase in dehydroepiandrosterone was associated with a decrease in testosterone levels in the hypothalamus of GF mice. Our findings suggest that the absence of microbes affects the neuroactive steroids in the periphery and the brain, supporting the evidence of a microbiota-mediated modulation of neuroendocrine pathways involved in preserving host brain functioning. Full article

(This article belongs to the Special Issue New Research on Endocrine Regulation of Brain Development)

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Review

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23 pages, 1661 KiB

Open AccessReview

The Epigenetic Role of Vitamin C in Neurodevelopment

by Sharna J. Coker, Carlos C. Smith-Díaz, Rebecca M. Dyson, Margreet C. M. Vissers and Mary J. Berry

Int. J. Mol. Sci. 2022, 23(3), 1208; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031208 - 21 Jan 2022

Cited by 18 | Viewed by 5470

Abstract

The maternal diet during pregnancy is a key determinant of offspring health. Early studies have linked poor maternal nutrition during gestation with a propensity for the development of chronic conditions in offspring. These conditions include cardiovascular disease, type 2 diabetes and even compromised mental health. While multiple factors may contribute to these outcomes, disturbed epigenetic programming during early development is one potential biological mechanism. The epigenome is programmed primarily in utero, and during this time, the developing fetus is highly susceptible to environmental factors such as nutritional insults. During neurodevelopment, epigenetic programming coordinates the formation of primitive central nervous system structures, neurogenesis, and neuroplasticity. Dysregulated epigenetic programming has been implicated in the aetiology of several neurodevelopmental disorders such as Tatton-Brown-Rahman syndrome. Accordingly, there is great interest in determining how maternal nutrient availability in pregnancy might affect the epigenetic status of offspring, and how such influences may present phenotypically. In recent years, a number of epigenetic enzymes that are active during embryonic development have been found to require vitamin C as a cofactor. These enzymes include the ten-eleven translocation methylcytosine dioxygenases (TETs) and the Jumonji C domain-containing histone lysine demethylases that catalyse the oxidative removal of methyl groups on cytosines and histone lysine residues, respectively. These enzymes are integral to epigenetic regulation and have fundamental roles in cellular differentiation, the maintenance of pluripotency and development. The dependence of these enzymes on vitamin C for optimal catalytic activity illustrates a potentially critical contribution of the nutrient during mammalian development. These insights also highlight a potential risk associated with vitamin C insufficiency during pregnancy. The link between vitamin C insufficiency and development is particularly apparent in the context of neurodevelopment and high vitamin C concentrations in the brain are indicative of important functional requirements in this organ. Accordingly, this review considers the evidence for the potential impact of maternal vitamin C status on neurodevelopmental epigenetics. Full article

(This article belongs to the Special Issue New Research on Endocrine Regulation of Brain Development)

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