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Allopregnanolone

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https://www.readbyqxmd.com/read/28905487/endogenous-neurosteroids-influence-synaptic-gabaa-receptors-during-post-natal-development
#1
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/28900387/social-isolation-in-early-versus-late-adolescent-mice-is-associated-with-persistent-behavioral-deficits-that-can-be-improved-by-neurosteroid-based-treatment
#2
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/28899788/the-translocator-protein-ligand-xbd173-improves-clinical-symptoms-and-neuropathological-markers-in-the-sjl-j-mouse-model-of-multiple-sclerosis
#3
Géraldine Leva, Christian Klein, Jérémie Benyounes, François Hallé, Frédéric Bihel, Nicolas Collongues, Jérôme De Seze, Ayikoe-Guy Mensah-Nyagan, Christine Patte-Mensah
Multiple sclerosis (MS) is a severe autoimmune disease characterized by inflammatory, demyelinating and neurodegenerative components causing motor, sensory, visual and/or cognitive symptoms. The relapsing-remitting MS affecting 85% of patients is reliably mimicked by the proteolipid-protein (PLP)-induced experimental autoimmune encephalomyelitis (EAE) SJL/J-mouse model. Significant progress was made for MS treatment but the development of effective therapies devoid of severe side-effects remains a great challenge...
September 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28894435/neuroactive-steroids-receptor-interactions-and-responses
#4
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/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
#5
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/28857628/correlation-between-allopregnanolone-levels-and-depressive-symptoms-during-late-menopausal-transition-and-early-postmenopause
#6
Radoslaw Slopien, Nicola Pluchino, Alina Warenik-Szymankiewicz, Stefan Sajdak, Michele Luisi, Panagiotis Drakopoulos, Andrea R Genazzani
OBJECTIVES: This observational, cross-sectional study included 140 women with climacteric symptoms. The aim of the study was to evaluate the correlation between the presence and severity of depressive symptoms and allopregnanolone levels in women during late menopausal transition and early postmenopause. METHODS: The study group was divided into two groups: 45 women in late menopausal transition and 95 early postmenopausal women. We evaluated Kupperman index, Hamilton scale and serum follicle-stimulating hormone, luteinizing hormone, 17β-estradiol, prolactin, total testosterone, dehydroepiandrosterone sulfate and allopregnanolone levels...
August 31, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/28852375/schwann-cell-development-maturation-and-regeneration-a-focus-on-classic-and-emerging-intracellular-signaling-pathways
#7
REVIEW
Luca Franco Castelnovo, Veronica Bonalume, Simona Melfi, Marinella Ballabio, Deborah Colleoni, Valerio Magnaghi
The development, maturation and regeneration of Schwann cells (SCs), the main glial cells of the peripheral nervous system, require the coordinate and complementary interaction among several factors, signals and intracellular pathways. These regulatory molecules consist of integrins, neuregulins, growth factors, hormones, neurotransmitters, as well as entire intracellular pathways including protein-kinase A, C, Akt, Erk/MAPK, Hippo, mTOR, etc. For instance, Hippo pathway is overall involved in proliferation, apoptosis, regeneration and organ size control, being crucial in cancer proliferation process...
July 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28799516/antiepileptic-drugs-in-clinical-development-differentiate-or-die
#8
Gaetano Zaccara, D Schmidt
BACKGROUND: Animal models when carefully selected, designed and conducted, are important parts of any translational drug development strategy. However, research of new compounds for patients with drug-resistant epilepsies is still based on animal experiments, mostly in rodents, which are far from being a model of chronic human epilepsy and have failed to differentiate the efficacy of new compounds versus standard drug treatment. Objective The objective was identification and description of compounds in clinical development in 2016...
August 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28743598/decrease-in-endogenous-brain-allopregnanolone-induces-autism-spectrum-disorder-asd-like-behavior-in-mice-a-novel-animal-model-of-asd
#9
Ken Ebihara, Hironori Fujiwara, Suresh Awale, Dya Fita Dibwe, Ryota Araki, Takeshi Yabe, Kinzo Matsumoto
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with core symptoms of social impairments and restrictive repetitive behaviors. Recent evidence has implicated a dysfunction in the GABAergic system in the pathophysiology of ASD. We investigated the role of endogenous allopregnanolone (ALLO), a neurosteroidal positive allosteric modulator of GABAA receptors, in the regulation of ASD-like behavior in male mice using SKF105111 (SKF), an inhibitor of type I and type II 5α-reductase, a rate-limiting enzyme of ALLO biosynthesis...
July 22, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28740098/puerarin-ameliorated-the-behavioral-deficits-induced-by-chronic-stress-in-rats
#10
Zhi-Kun Qiu, Guan-Hua Zhang, De-Sheng Zhong, Jia-Li He, Xu Liu, Ji-Sheng Chen, Da-Nian Wei
The present study aimed to investigate the mechanisms underlying the antidepressant-like effects of puerarin via the chronic unpredictable stress (CUS) procedure in rats. Similar to Sertraline (Ser), Chronic treatment of puerarin (60 and 120 mg/kg, i.g) elicited the antidepressant-like effects by reversing the decreased sucrose preference in sucrose preference test (SPT), by blocking the increased latency to feed in novelty-suppressed feeding test (NSFT) and the increased immobility time in forced swimming test (FST) without affecting locomotor activity...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715875/acute-orexigenic-effect-of-agmatine-involves-interaction-between-central-%C3%AE-2-adrenergic-and-gabaergic-receptors
#11
Brijesh Gulabrao Taksande, Omi Sharma, Manish Manohar Aglawe, Mayur Bhimrao Kale, Dinesh Yugraj Gawande, Milind Janraoji Umekar, Nandkishor Ramdas Kotagale
Agmatine and GABA have been abundantly expressed in brain nuclei involved in regulation of energy homeostasis and promoting stimulation of food intake in rodents. However, their mutual interaction, if any, in the elicitation of feeding behavior is largely remains unclear. The current study provides experimental evidence for the possible interaction of agmatine, adrenergic and GABAergic systems in stimulation of feeding in satiated rats. Satiated rats fitted with intracerebroventricular (i.c.v.) cannulae and were administered agmatine, alone or jointly with (a) GABAA receptor agonist, muscimol, diazepam or antagonist bicuculline and flumazenil, GABAA positive modulator, allopregnanolone or negative modulator of GABAA receptor, dehydroepiandrosterone (b) In view of the high affinity of agmatine for α2-adrenoceptors and the close association between α2-adrenoceptors and GABAergic system, the effect of their modulators on feeding elicited by agmatine/GABAergic agonists were also examined...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28707277/open-label-allopregnanolone-treatment-of-men-with-fragile-x-associated-tremor-ataxia-syndrome
#12
J Y Wang, A M Trivedi, N R Carrillo, J Yang, A Schneider, C Giulivi, P Adams, F Tassone, K Kim, S M Rivera, N Lubarr, C-Y Wu, R W Irwin, R D Brinton, J M Olichney, M A Rogawski, R J Hagerman
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder affecting approximately 45% of male and 16% of female carriers of the FMR1 premutation over the age of 50 years. Currently, no effective treatment is available. We performed an open-label intervention study to assess whether allopregnanolone, a neurosteroid promoting regeneration and repair, can improve clinical symptoms, brain activity, and magnetic resonance imaging (MRI) measurements in patients with FXTAS. Six patients underwent weekly intravenous infusions of allopregnanolone (2-6 mg over 30 min) for 12 weeks...
July 13, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28694181/allopregnanolone-involvement-in-feeding-regulation-overeating-and-obesity
#13
E Holmberg, J Sjöstedt, E Malinina, M Johansson, S Turkmen, G Ragagnin, A Lundqvist, M Löfgren, L Jaukkuri, M Bixo, T Bäckström
Obesity is strongly associated with ill health, primarily caused by consumption of excessive calories, and promoted (inter alia) by gamma-amino-butyric-acid (GABA) stimulating food intake by activating GABAA receptors (primarily with α3 and α2 subunits) in the hypothalamic arcuate nucleus and paraventricular nucleus. Allopregnanolone is a potent positive GABAA receptor modulating steroid (GAMS). As reviewed here, elevated allopregnanolone levels are associated with increases in food intake, preferences for energy-rich food, and obesity in humans and other mammals...
July 8, 2017: Frontiers in Neuroendocrinology
https://www.readbyqxmd.com/read/28667781/translocator-protein-18-kda-an-update-on-its-function-in-steroidogenesis
#14
REVIEW
Vassilios Papadopoulos, Jinjiang Fan, Barry Zirkin
Translocator protein (18 kDa), TSPO, is a ubiquitous mitochondrial protein. Studies of its responses to drug and endogenous ligands have shown TSPO to be involved either directly or indirectly in numerous biological functions, including mitochondrial cholesterol transport and steroid hormone biosynthesis, porphyrin transport and heme synthesis, apoptosis, cell proliferation, and anion transport. Localized to the outer mitochondrial membrane of steroidogenic cells, TSPO has been shown to associate with cytosolic and mitochondrial proteins as part of a large multiprotein complex involved in mitochondrial cholesterol transport, the rate-limiting step in steroidogenesis...
July 1, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28667510/a-randomized-controlled-trial-of-ganaxolone-in-posttraumatic-stress-disorder
#15
Ann M Rasmusson, Christine E Marx, Sonia Jain, Gail M Farfel, Julia Tsai, Xiaoying Sun, Thomas D Geracioti, Mark B Hamner, James Lohr, Richard Rosse, Lanier Summerall, Jennifer C Naylor, Cristine Cusin, Ariel J Lang, Rema Raman, Murray B Stein
Preclinical and clinical research supports a role for neuroactive steroids in the pathophysiology of posttraumatic stress disorder (PTSD). We investigated ganaxolone (a synthetic 3β-methylated derivative of allopregnanolone, a GABAergic neuroactive steroid) for treatment of PTSD in a proof-of-concept, multisite, double-blind, placebo-controlled trial. Veteran and non-veteran participants (n = 112) were randomized to ganaxolone or placebo at biweekly escalating doses of 200, 400, and 600 mg twice daily for 6 weeks...
August 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28666923/allopregnanolone-levels-and-depressive-symptoms-during-pregnancy-in-relation-to-single-nucleotide-polymorphisms-in-the-allopregnanolone-synthesis-pathway
#16
Charlotte Hellgren, Erika Comasco, Alkistis Skalkidou, Inger Sundström-Poromaa
Allopregnanolone, a neurosteroid whose levels rise throughout gestation, putatively stabilizes antenatal mood. The present study aimed to investigate associations of plasma allopregnanolone to antenatal depressive symptoms, as well as to genetic and obstetric factors. Allopregnanolone plasma levels from 284 pregnant women were measured around gestational week 18. Haplotype tag single nucleotide polymorphisms in the aldo-keto reductase family 1, members C2 and C4 (AKR1C2, AKR1C4), and steroid 5 alpha-reductase 1 and 2 (SRD5A1, and SRD5A2) genes were genotyped in a larger sample of pregnant women (n=1351)...
July 20, 2017: Hormones and Behavior
https://www.readbyqxmd.com/read/28664280/ethanol-withdrawal-induced-dysregulation-of-neurosteroid-levels-in-plasma-cortex-and-hippocampus-in-genetic-animal-models-of-high-and-low-withdrawal
#17
Jeremiah P Jensen, Michelle A Nipper, Melinda L Helms, Matthew M Ford, John C Crabbe, David J Rossi, Deborah A Finn
RATIONALE: Endogenous γ-aminobutyric acidA receptor (GABAAR)-active neurosteroids (e.g., allopregnanolone) regulate central nervous system excitability and many physiological functions, so fluctuations are implicated in several neuropsychiatric disorders. Pertinently, evidence supports an inverse relationship between endogenous GABAAR-active neurosteroid levels and behavioral changes in excitability during ethanol withdrawal (WD). OBJECTIVES: The present studies determined mouse genotype differences in ten neurosteroid levels in plasma, cortex, and hippocampus over the time course of ethanol WD in the WD Seizure-Prone (WSP) and WD Seizure-Resistant (WSR) selected lines and in the DBA/2J (DBA) inbred strain...
June 29, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28655607/overexpression-of-the-18%C3%A2-kda-translocator-protein-tspo-in-the-hippocampal-dentate-gyrus-produced-anxiolytic-and-antidepressant-like-behavioural-effects
#18
Lei Li, Wei Wang, Li-Ming Zhang, Xiang-Yun Jiang, Shu-Zheng Sun, Li-Jun Sun, Ying Guo, Jie Gong, You-Zhi Zhang, Heng-Lin Wang, Yun-Feng Li
The 18 kDa translocator protein (TSPO) is a five transmembrane domain protein that plays a crucial role in neurosteroid (e.g., allopregnanolone) synthesis by promoting the transport of cholesterol to the inner mitochondrial membrane. This protein is predominantly expressed in steroid-synthesizing tissues, including the central and peripheral nervous system, affecting stress-related disorders such as anxiety and depression. Recent studies have focused on the hippocampal dentate gyrus, which is very important for involvement of anxiety and depression...
June 24, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28631553/administration-of-progesterone-throughout-pregnancy-increases-maternal-steroids-without-adverse-effect-on-mature-oligodendrocyte-immunostaining-in-the-guinea-pig
#19
Julia C Shaw, Hannah K Palliser, Kerrin Palazzi, Jonathan J Hirst
Progesterone is administered to pregnant women at risk of premature labor, despite systematic reviews showing conflicting outcomes regarding its use, highlighting doubt over the effectiveness of the therapy. Progesterone can be rapidly metabolized into a number of steroids, but to date, there has been a lack of investigation into the fetal steroid profiles following administration and whether this impacts fetal neurodevelopment. The objective of this study was to determine the effect of progesterone treatment on allopregnanolone and cortisol levels in the fetus and on a marker of myelination in the fetal brain...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28623385/juvenile-social-isolation-affects-maternal-care-in-rats-involvement-of-allopregnanolone
#20
Maria Giuseppina Pisu, Giorgia Boero, Francesca Biggio, Anna Garau, Daniela Corda, Mauro Congiu, Alessandra Concas, Patrizia Porcu, Mariangela Serra
RATIONALE: Social isolation of rats immediately after weaning is thought to represent an animal model of anxiety-like disorders. Socially isolated virgin females showed a significant decrease in allopregnanolone levels, associated with increased anxiety-related behavior compared with group-housed rats. OBJECTIVES: The present study investigates whether post-weaning social isolation affects maternal behavior and assesses neuroactive steroid levels in adult female rats during pregnancy and postpartum...
June 16, 2017: Psychopharmacology
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