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Biomolecules
Special Issues
Neurosteroids in Health and Disease
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Neurosteroids in Health and Disease

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biomacromolecules: Lipids".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 12917

Special Issue Editor

Dr. Hana Kubova

E-Mail Website
Guest Editor
Developmental Epileptology, Institute of Physiology of the Czech Academy of Sciences, Czech Republic
Interests: mechanisms of ictogenesis; mechanisms of epileptogenesis; long term impact of early brain injury; long term impact of early exposure to neuroactive (antiepileptic) drugs; developmental pharmacology; biomarkers of epileptogenesis

Special Issue Information

Dear Colleagues,

Neurosteroids are potent endogenous neuromodulators with rapid actions in the central nervous system via non-genomic mechanisms by modulation neurotransmission. They exert their action already at low concentrations and they may act on different neurotransmitter pathways. Neurosteroids play a specific role in various normal or pathological brain functions. Wide spectrum of their effects suggests promising therapeutic potential of these compounds. Absence or reduced concentrations of neurosteroids during development may be associated with various neurodevelopmental and neuropsychiatric disorders like anxiety disorders, schizophrenia, epilepsy, stress or Alzheimer disease. In physiologic or pharmacologic concentrations neurosteroids may also promote neurogenesis, neuronal survival, myelination, improve memory, and reduce neurotoxicity. Neuroactive steroids, synthetic analogues of neurosteroids, have several advantages over natural neurosteroids for clinical use, because their superior bioavailability, pharmacokinetics and safety profiles.

For this Special Issue titled “Neurosteroids in health and disease”, we are looking for original research articles and state-of-the-art reviews on neurosteroids in health and disease, their role in neurodevelopment and therapeutic potential of neurosteroids and their synthetic analogues in neuropsychiatric disorders that contribute to the understanding of the underlying molecular mechanisms of their action or a possible use for the diagnosis and prognosis of disease and individuals’ responses to therapies.

Dr. Hana Kubova
Guest Editor

Manuscript Submission Information

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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. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • Neurosteroid
  • Neuroactive steroids
  • Brain development
  • Mechanisms of action
  • Physiological role
  • Role in pathogenesis

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Published Papers (4 papers)

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Research

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24 pages, 1259 KiB  
Article
Altered Steroidome in Women with Gestational Diabetes Mellitus: Focus on Neuroactive and Immunomodulatory Steroids from the 24th Week of Pregnancy to Labor
by Leona Ondřejíková, Antonín Pařízek, Patrik Šimják, Daniela Vejražková, Marta Velíková, Kateřina Anderlová, Michala Vosátková, Hana Krejčí, Michal Koucký, Radmila Kancheva, Michaela Dušková, Markéta Vaňková, Josef Bulant and Martin Hill
Biomolecules 2021, 11(12), 1746; https://doi.org/10.3390/biom11121746 - 23 Nov 2021
Cited by 3 | Viewed by 2305
Abstract
Gestational diabetes mellitus (GDM) is a complication in pregnancy, but studies focused on the steroidome in patients with GDM are not available in the public domain. This article evaluates the steroidome in GDM+ and GDM− women and its changes from 24 weeks (± [...] Read more.
Gestational diabetes mellitus (GDM) is a complication in pregnancy, but studies focused on the steroidome in patients with GDM are not available in the public domain. This article evaluates the steroidome in GDM+ and GDM− women and its changes from 24 weeks (± of gestation) to labor. The study included GDM+ (n = 44) and GDM− women (n = 33), in weeks 24–28, 30–36 of gestation and at labor and mixed umbilical blood after delivery. Steroidomic data (101 steroids quantified by GC-MS/MS) support the concept that the increasing diabetogenic effects with the approaching term are associated with mounting progesterone levels. The GDM+ group showed lower levels of testosterone (due to reduced AKR1C3 activity), estradiol (due to a shift from the HSD17B1 towards HSD17B2 activity), 7-oxygenated androgens (competing with cortisone for HSD11B1 and shifting the balance from diabetogenic cortisol towards the inactive cortisone), reduced activities of SRD5As, and CYP17A1 in the hydroxylase but higher CYP17A1 activity in the lyase step. With the approaching term, the authors found rising activities of CYP3A7, AKR1C1, CYP17A1 in its hydroxylase step, but a decline in its lyase step, rising conjugation of neuroinhibitory and pregnancy-stabilizing steroids and weakening AKR1D1 activity. Full article
(This article belongs to the Special Issue Neurosteroids in Health and Disease)
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22 pages, 2519 KiB  
Article
Pitfalls of NMDA Receptor Modulation by Neuroactive Steroids. The Effect of Positive and Negative Modulation of NMDA Receptors in an Animal Model of Schizophrenia
by Kristina Holubova, Marketa Chvojkova, Barbora Hrcka Krausova, Vojtech Vyklicky, Eva Kudova, Hana Chodounska, Ladislav Vyklicky and Karel Vales
Biomolecules 2021, 11(7), 1026; https://doi.org/10.3390/biom11071026 - 14 Jul 2021
Cited by 5 | Viewed by 3080
Abstract
Evidence from clinical and preclinical studies implicates dysfunction of N-methyl-D-aspartate receptors (NMDARs) in schizophrenia progression and symptoms. We investigated the antipsychotic effect of two neuroactive steroids in an animal model of schizophrenia induced by systemic application of MK-801. The neuroactive [...] Read more.
Evidence from clinical and preclinical studies implicates dysfunction of N-methyl-D-aspartate receptors (NMDARs) in schizophrenia progression and symptoms. We investigated the antipsychotic effect of two neuroactive steroids in an animal model of schizophrenia induced by systemic application of MK-801. The neuroactive steroids differ in their mechanism of action at NMDARs. MS-249 is positive, while PA-Glu is a negative allosteric NMDAR modulator. We hypothesized that the positive NMDA receptor modulator would attenuate deficits caused by MK-801 co-application more effectively than PA-Glu. The rats were tested in a battery of tests assessing spontaneous locomotion, anxiety and cognition. Contrary to our expectations, PA-Glu exhibited a superior antipsychotic effect to MS-249. The performance of MS-249-treated rats in cognitive tests differed depending on the level of stress the rats were exposed to during test sessions. In particular, with the increasing severity of stress exposure, the performance of animals worsened. Our results demonstrate that enhancement of NMDAR function may result in unspecific behavioral responses. Positive NMDAR modulation can influence other neurobiological processes besides memory formation, such as anxiety and response to stress. Full article
(This article belongs to the Special Issue Neurosteroids in Health and Disease)
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9 pages, 1350 KiB  
Article
Epipregnanolone as a Positive Modulator of GABAA Receptor in Rat Cerebellar and Hippocampus Neurons
by Julia Bukanova, Elena Solntseva, Rodion Kondratenko and Eva Kudova
Biomolecules 2021, 11(6), 791; https://doi.org/10.3390/biom11060791 - 24 May 2021
Cited by 6 | Viewed by 2319
Abstract
Epipregnanolone (3β-hydroxy-5β-pregnan-20-one, Epi) is an endogenous steroid with important physiological effects and high affinity for GABAA receptors. The effect of Epi on GABA-induced chloride current (IGABA) in native neurons has hardly been studied. In this work, we studied the [...] Read more.
Epipregnanolone (3β-hydroxy-5β-pregnan-20-one, Epi) is an endogenous steroid with important physiological effects and high affinity for GABAA receptors. The effect of Epi on GABA-induced chloride current (IGABA) in native neurons has hardly been studied. In this work, we studied the influence of Epi on the IGABA in the Purkinje cells of rat cerebellum and pyramidal neurons of rat hippocampus with the patch clamp technique. We showed that Epi is a positive modulator of the IGABA with EC50 of 5.7 µM in Purkinje cells and 9.3 µM in hippocampal neurons. Epi-induced potentiation of the IGABA was more potent at low vs. high GABA concentrations. Isopregnanolone (3β-hydroxy-5α-pregnan-20-one, Iso) counteracted Epi, reducing its potentiating effect by 2–2.3 times. Flumazenil, a nonsteroidal GABAA receptor antagonist, does not affect the Epi-induced potentiation. Comparison of the potentiating effects of Epi and allopregnanolone (3α-hydroxy-5α-pregnan-20-one, ALLO) showed that ALLO is, at least, a four times more potent positive modulator than Epi. The combined application of ALLO and Epi showed that the effects of these two steroids are not additive. We conclude that Epi has a dual effect on the IGABA increasing the current in the control solution and decreasing the stimulatory effect of ALLO. Full article
(This article belongs to the Special Issue Neurosteroids in Health and Disease)
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Review

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23 pages, 6806 KiB  
Review
Analytical Methods for the Determination of Neuroactive Steroids
by Michal Kaleta, Jana Oklestkova, Ondřej Novák and Miroslav Strnad
Biomolecules 2021, 11(4), 553; https://doi.org/10.3390/biom11040553 - 9 Apr 2021
Cited by 17 | Viewed by 3885
Abstract
Neuroactive steroids are a family of all steroid-based compounds, of both natural and synthetic origin, which can affect the nervous system functions. Their biosynthesis occurs directly in the nervous system (so-called neurosteroids) or in peripheral endocrine tissues (hormonal steroids). Steroid hormone levels may [...] Read more.
Neuroactive steroids are a family of all steroid-based compounds, of both natural and synthetic origin, which can affect the nervous system functions. Their biosynthesis occurs directly in the nervous system (so-called neurosteroids) or in peripheral endocrine tissues (hormonal steroids). Steroid hormone levels may fluctuate due to physiological changes during life and various pathological conditions affecting individuals. A deeper understanding of neuroactive steroids’ production, in addition to reliable monitoring of their levels in various biological matrices, may be useful in the prevention, diagnosis, monitoring, and treatment of some neurodegenerative and psychiatric diseases. The aim of this review is to highlight the most relevant methods currently available for analysis of neuroactive steroids, with an emphasis on immunoanalytical methods and gas, or liquid chromatography combined with mass spectrometry. Full article
(This article belongs to the Special Issue Neurosteroids in Health and Disease)
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