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https://www.readbyqxmd.com/read/28919448/review-7%C3%AE-hydroxypregnenolone-regulating-locomotor-behavior-identified-in-the-brain-and-pineal-gland-across-vertebrates
#1
REVIEW
Kazuyoshi Tsutsui, Shogo Haraguchi, Hubert Vaudry
The brain synthesizes steroids de novo from cholesterol, which are called neurosteroids. Based on extensive studies on neurosteroids over the past thirty years, it is now accepted that neurosteroidogenesis in the brain is a conserved property across vertebrates. However, the formation of bioactive neurosteroids in the brain is still incompletely elucidated in vertebrates. In fact, we recently identified 7 α -hydroxypregnenolone (7 α -OH PREG) as a novel bioactive neurosteroid stimulating locomotor behavior in the brain of several vertebrates...
September 14, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28905487/endogenous-neurosteroids-influence-synaptic-gabaa-receptors-during-post-natal-development
#2
REVIEW
Delia Belelli, Adam R Brown, Scott J Mitchell, Ben G Gunn, Murray B Herd, Grant Phillips, Mohsen Seifi, Jerome D Swinny, Jeremy J Lambert
GABA plays a key role in both embryonic and neonatal brain development. For example, during early neonatal nervous system maturation, synaptic transmission, mediated by GABAA receptors (GABAA Rs), undergoes a temporally specific form of synaptic plasticity, to accommodate the changing requirements of maturing neural networks. Specifically, the duration of miniature inhibitory postsynaptic currents (mIPSCs), resulting from vesicular GABA activating synaptic GABAA Rs, is reduced, permitting neurons to appropriately influence the window for postsynaptic excitation...
September 14, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28901728/gaba-type-a-receptor-trafficking-and-the-architecture-of-synaptic-inhibition
#3
REVIEW
Joshua M Lorenz-Guertin, Tija C Jacob
Ubiquitous expression of GABA type A receptors (GABAA R) in the central nervous system establishes their central role in coordinating most aspects of neural function and development. Dysregulation of GABAergic neurotransmission manifests in a number of human health disorders and conditions that in certain cases can be alleviated by drugs targeting these receptors. Precise changes in the quantity or activity of GABAA Rs localized at the cell surface and at GABAergic postsynaptic sites directly impact the strength of inhibition...
September 13, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28900387/social-isolation-in-early-versus-late-adolescent-mice-is-associated-with-persistent-behavioral-deficits-that-can-be-improved-by-neurosteroid-based-treatment
#4
Andrea Locci, Philippe Geoffroy, Michel Miesch, Ayikoe-Guy Mensah-Nyagan, Graziano Pinna
Early trauma and stress exposure during a critical period of life may increase the risk of major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) in adulthood. The first-choice treatment for MDD and PTSD are selective serotonin reuptake inhibitor (SSRI) antidepressants. Unfortunately, half of MDD and PTSD patients show resistance to the therapeutic effects of these drugs and more efficient treatments are essential. Both MDD and PTSD patients present reduced levels of allopregnanolone (Allo), a potent endogenous positive allosteric modulator of GABA action at GABAA receptors which are normalized by SSRIs in treatment responders...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28894435/neuroactive-steroids-receptor-interactions-and-responses
#5
REVIEW
Kald Beshir Tuem, Tesfay Mehari Atey
Neuroactive steroids (NASs) are naturally occurring steroids, which are synthesized centrally as de novo from cholesterol and are classified as pregnane, androstane, and sulfated neurosteroids (NSs). NASs modulate many processes via interacting with gamma-aminobutyric acid (GABA), N-methyl-d-aspartate, serotonin, voltage-gated calcium channels, voltage-dependent anion channels, α-adrenoreceptors, X-receptors of the liver, transient receptor potential channels, microtubule-associated protein 2, neurotrophin nerve growth factor, and σ1 receptors...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28893622/differential-expression-of-vitamin-d-associated-enzymes-and-receptors-in-brain-cell-subtypes
#6
Véréna Landel, Delphine Stephan, Xiaoying Cui, Darryl Eyles, François Feron
Accumulating evidence indicates that the active form of vitamin D, 1,25(OH)2D3, can be considered as a neurosteroid. However, the cerebral expression of vitamin D-associated enzymes and receptors remains controversial. With the idea of carrying out a comparative study in mind, we compared the transcript expression of Cyp27a1, Cyp27b1, Cyp24a1, Vdr and Pdia3 in purified cultures of astrocytes, endothelial cells, microglia, neurons and oligodendrocytes. We observed that endothelial cells and neurons can possibly transform the inactive cholecalciferol into 25(OH)D3...
September 8, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28893591/neurosteroid-dehydroepiandrosterone-improves-active-avoidance-retrieval-and-induces-antidepressant-like-behavior-in-rats
#7
Janko Samardzic, Boris Hencic, Jasna Jancic, Dragana Jadzic, Milos Djuric, Dragan I Obradovic, Dubravka Svob Strac
Various studies reported beneficial effects of dehydroepiandrosterone (DHEA) and its sulphate (DHEAS), the neurosteroids involved in various brain functions, on synaptic plasticity, neuronal survival, memory, learning and behavior. This study aimed to investigate the behavioral profile of acute DHEA treatment by using active avoidance (AA) task, primarily predictive of the effects on the retrieval-based learning, and by applying forced swim test (FST), for assessment of antidepressant-like potential. Adult male Wistar rats received intraperitoneal injections of either DHEA (2, 10, 20mg/kg) or solvent, 30min prior to testing...
September 8, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28891264/hormonal-and-genetic-factors-interact-to-control-aromatase-expression-in-the-developing-brain
#8
REVIEW
Carla Daniela Cisternas, Luis Miguel Garcia-Segura, María Julia Cambiasso
The brain expression of the enzyme P450-aromatase has been extensively studied. Since the aromatization hypothesis established brain aromatase as a key factor to convert gonadal testosterone to oestradiol, several studies have investigated the regulation of aromatase during the critical period of brain sexual differentiation. Here, we review previous and recent findings concerning regulation of aromatase. The role of gonadal hormones, sex chromosome genes and neurosteroids is analysed in term of their contribution to aromatase expression and the implications for the organizational effect of steroids during development...
September 10, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28890368/cyp17a1-independent-production-of-the-neurosteroid-derived-5%C3%AE-pregnan-3%C3%AE-6%C3%AE-diol-20-one-in-androgen-responsive-prostate-cancer-cell-lines-under-serum-starvation-and-inhibition-by-abiraterone
#9
Antonio G Gomes de Mello Martins, Giuseppe Allegretta, Gerhard Unteregger, Jörg Haupenthal, Jens Eberhard, Michael Hoffmann, Jill A van der Zee, Kerstin Junker, Michael Stöckle, Rolf Müller, Rolf W Hartmann, Carsten-H Ohlmann
CYP17A1-independent intratumoral steroid hormone synthesis is regarded as one possible explanation for resistance to treatment with the CYP17-inhibitor Abiraterone (Abi). The aim of our study was therefore to investigate the steroid metabolism of prostate cancer cells under serum starvation and the effects of Abi treatment. We assessed steroid metabolism in a panel of prostate cancer cells under serum starvation by radioactivity detector-coupled HPLC and HPLC-ESI-ToF-mass spectrometry after treatment with pregnenolone, progesterone and allopregnanolone...
September 7, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28884425/can-a-neurosteroid-ameliorate-fragile-x-associated-tremor-ataxia-syndrome
#10
EDITORIAL
Dejan B Budimirovic
No abstract text is available yet for this article.
September 7, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28883994/lipidomics-of-human-umbilical-cord-serum-identification-of-unique-sterol-sulfates
#11
Paul L Wood, Heli Siljander, Mikael Knip
AIM: There are currently limited lipidomics data for human umbilical cord blood. Therefore, the lipidomes of cord sera from six newborns and sera from six nonpregnant females were compared. MATERIALS & METHODS: Sera lipidomics analyses were conducted using a high-resolution mass spectrometry analytical platform. RESULTS: Cord serum contained a diverse array of glycerophospholipids, albeit generally at lower concentrations than monitored in adult serum...
August 2017: Future Science OA
https://www.readbyqxmd.com/read/28878622/ganaxolone-a-new-treatment-for-neonatal-seizures
#12
REVIEW
Tamara Yawno, Suzie L Miller, Laura Bennet, Flora Wong, Jonathan J Hirst, Michael Fahey, David W Walker
Neonatal seizures are amongst the most common neurologic conditions managed by a neonatal care service. Seizures can exacerbate existing brain injury, induce "de novo" injury, and are associated with neurodevelopmental disabilities in post-neonatal life. In this mini-review, we present evidence in support of the use of ganaxolone, a GABA(A) agonist neurosteroid, as a novel neonatal therapy. We discuss evidence that ganaxolone can provide both seizure control and neuroprotection with a high safety profile when administered early following birth-related hypoxia, and show evidence that it is likely to prevent or reduce the incidence of the enduring disabilities associated with preterm birth, cerebral palsy, and epilepsy...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28875337/clinical-and-molecular-analysis-of-6-chinese-patients-with-isoleucine-metabolism-defects-identification-of-3-novel-mutations-in-the-hsd17b10-and-acat1-gene
#13
Ling Su, Xiuzhen Li, Ruizhu Lin, Huiying Sheng, Zhichun Feng, Li Liu
Hydroxysteroid (17β) dehydrogenase 10 (HSD10) and mitochondrial acetoacetyl-CoA thiolase (β-KT) are two adjacent enzymes for the degradation of isoleucine, thus HSD10 and β-KT deficiencies are confusing at an early stage because of nearly the same elevation of typical metabolites in urine, such as 2-methyl-3-hydroxybutyric acid (2M3HBA) and tiglylglycine (TG). In order to better understand the differences between these two disorders, we described the clinical and molecular characteristics of two HSD10 deficiency patients and four β-KT deficiency patients...
September 5, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28872596/survey-of-veterinarians-using-a-novel-physical-compression-squeeze-procedure-in-the-management-of-neonatal-maladjustment-syndrome-in-foals
#14
Monica Aleman, Kalie M Weich, John E Madigan
Horses are a precocious species that must accomplish several milestones that are critical to survival in the immediate post-birth period for their survival. One essential milestone is the successful transition from the intrauterine unconsciousness to an extrauterine state of consciousness or awareness. This transition involves a complex withdrawal of consciousness inhibitors and an increase in neuroactivating factors that support awareness. This process involves neuroactive hormones as well as inputs related to factors such as cold, visual, olfactory, and auditory stimuli...
September 5, 2017: Animals: An Open Access Journal From MDPI
https://www.readbyqxmd.com/read/28866326/progesterone-improves-neurocognitive-outcomes-following-therapeutic-cranial-irradiation-in-mice
#15
Seema Yousuf, Daniel J Brat, Hui-Kuo Shu, Ya Wang, Donald G Stein, Fahim Atif
Despite improved therapeutic methods, CNS toxicity resulting from cancer treatment remains a major cause of post-treatment morbidity. More than half of adult patients with cranial irradiation for brain cancer develop neurobehavioral/cognitive deficits that severely impact quality of life. We examined the neuroprotective effects of the neurosteroid progesterone (PROG) against ionizing radiation (IR)-induced neurobehavioral/cognitive deficits in mice. Male C57/BL mice were exposed to one of two fractionated dose regimens of IR (3Gy×3 or 3Gy×5)...
September 14, 2017: Hormones and Behavior
https://www.readbyqxmd.com/read/28863815/direct-interactions-of-cholesterol-with-pentameric-ligand-gated-ion-channels-testable-hypotheses-from-computational-predictions
#16
Grace Brannigan
Several essential ionotropic neurotransmitter receptors, including the nicotinic acetylcholine receptor (nAChR) and gamma-aminobutyric acid (GABA) type A receptor (GABAAr), belong to the family of pentameric ligand-gated ion channels (pLGICs). Function of these receptors is particularly sensitive to their lipid environment, including cholesterol and cholesterol-derived neurosteroids. Direct structural data investigating interactions between sterols and pLGICs, as well as their role in modulatory mechanisms, are largely unavailable...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28825714/cell-targetable-dna-nanocapsules-for-spatiotemporal-release-of-caged-bioactive-small-molecules
#17
Aneesh T Veetil, Kasturi Chakraborty, Kangni Xiao, Myles R Minter, Sangram S Sisodia, Yamuna Krishnan
Achieving triggered release of small molecules with spatial and temporal precision at designated cells within an organism remains a challenge. By combining a cell-targetable, icosahedral DNA-nanocapsule loaded with photoresponsive polymers, we show cytosolic delivery of small molecules with the spatial resolution of single endosomes in specific cells in Caenorhabditis elegans. Our technology can report on the extent of small molecules released after photoactivation as well as pinpoint the location at which uncaging of the molecules occurred...
August 21, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28825678/effects-of-refined-xiaoyaosan-on-depressive-like-behaviors-in-rats-with-chronic-unpredictable-mild-stress-through-neurosteroids-their-synthesis-and-metabolic-enzymes
#18
Xiaoling Guo, Wenqi Qiu, Yueyun Liu, Yifang Zhang, Hongbo Zhao, Jiaxu Chen
Abstract: To observe the effects of refined Xiaoyaosan (XYS) on the depressive-like behaviors in rats with chronic unpredictable mild stress (CUMS), and to explore the relationship between the changes of neurosteroids and mRNA expressions of their synthesis and metabolic enzymes, and the mechanism of XYS in the treatment of depression. Methods: Eighty-four healthy male Sprague-Dawley rats were randomly divided into normal group, model group, XYS group and fluoxetine group. The latter three groups were subjected to 21 days of CUMS to prepare the stress depression model...
August 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28812018/effects-of-fungicides-on-rat-s-neurosteroid-synthetic-enzymes
#19
Xiuwei Shen, Fan Chen, Lanlan Chen, Ying Su, Ping Huang, Ren-Shan Ge
Exposure to environmental endocrine disruptors may interfere with nervous system's activity. Fungicides such as tebuconazole, triadimefon, and vinclozolin have antifungal activities and are used to prevent fungal infections in agricultural plants. In the present study, we studied effects of tebuconazole, triadimefon, and vinclozolin on rat's neurosteroidogenic 5α-reductase 1 (5α-Red1), 3α-hydroxysteroid dehydrogenase (3α-HSD), and retinol dehydrogenase 2 (RDH2). Rat's 5α-Red1, 3α-HSD, and RDH2 were cloned and expressed in COS-1 cells, and effects of these fungicides on them were measured...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28803966/a-chimeric-prokaryotic-eukaryotic-pentameric-ligand-gated-ion-channel-reveals-interactions-between-the-extracellular-and-transmembrane-domains-shape-neurosteroid-modulation
#20
Borna Ghosh, Tzu-Wei Tsao, Cynthia Czajkowski
Pentameric ligand-gated ion channels (pLGICs) are the targets of several clinical and endogenous allosteric modulators including anesthetics and neurosteroids. Molecular mechanisms underlying allosteric drug modulation are poorly understood. Here, we constructed a chimeric pLGIC by fusing the extracellular domain (ECD) of the proton-activated, cation-selective bacterial channel GLIC to the transmembrane domain (TMD) of the human ρ1 chloride-selective GABAAR, and tested the hypothesis that drug actions are regulated locally in the domain that houses its binding site...
October 2017: Neuropharmacology
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