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Allopregnanolone

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https://www.readbyqxmd.com/read/29113830/sex-and-age-associated-differences-in-episodic-like-memory-and-transcriptional-regulation-of-hippocampal-steroidogenic-enzymes-in-rats
#1
María F Rossetti, Jorgelina Varayoud, María F Andreoli, Cora Stoker, Enrique H Luque, Jorge G Ramos
The aim of this study was to evaluate the episodic-like memory (ELM) and the transcriptional regulation of the enzymes involved in hippocampal allopregnanolone synthesis in young adult and middle-aged male and female rats. Young adult males, but not middle-aged ones, showed a good performance in the ELM task. In contrast, neither young nor middle-aged females were able to discriminate the spatial order in which the objects were presented. In females, aging decreased the transcription of steroidogenic-related genes...
November 4, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29112774/neuroactive-steroid-3%C3%AE-5%C3%AE-3-hydroxypregnan-20-one-3%C3%AE-5%C3%AE-thp-and-pro-inflammatory-cytokine-mcp-1-levels-in-hippocampus-ca1-are-correlated-with-voluntary-ethanol-consumption-in-cynomolgus-monkey
#2
Matthew C Beattie, Christopher S Reguyal, Patrizia Porcu, James B Daunais, Kathleen A Grant, A Leslie Morrow
BACKGROUND: Neuroactive steroids such as (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone) are potent neuromodulators that enhance GABAergic neurotransmission and produce inhibitory neurobehavioral and anti-inflammatory effects. Chronic ethanol consumption reduces 3α,5α-THP levels in human plasma, but has brain-region and species-specific effects on CNS levels of 3α,5α-THP. We explored the relationship between 3α,5α-THP levels in the hippocampus and voluntary ethanol consumption in the cynomolgus monkey following daily self-administration of ethanol for 12 months and further examined the relationship to HPA axis function prior to ethanol exposure...
November 7, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29101599/the-anxiolytic-like-effects-of-puerarin-are-associated-with-the-changes-of-monoaminergic-neurotransmitters-and-biosynthesis-of-allopregnanolone-in-the-brain
#3
Zhi-Kun Qiu, De-Sheng Zhong, Jia-Li He, Xu Liu, Ji-Sheng Chen, Hong Nie
Anxiety disorder is a serious and burdensome psychiatric illness that frequently turn into chronic clinical conditions. Puerarin have been shown to be effective in the therapy of depression. However, few studies are concerned about the anxiolytic-like effects of puerarin. The current study aimed to evaluate the anxiolytic-like effects of puerarin and its possible mechanism. To evaluate this, the behavioral tests, i.e. Vogel-type conflict test (VTCT), elevated plus-maze test (EPMT), and open-field test (OFT) were conducted...
November 3, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29090684/neuroactive-steroids-and-affective-symptoms-in-women-across-the-weight-spectrum
#4
Laura E Dichtel, Elizabeth A Lawson, Melanie Schorr, Erinne Meenaghan, Margaret Lederfine Paskal, Kamryn T Eddy, Graziano Pinna, Marianela Nelson, Ann M Rasmusson, Anne Klibanski, Karen K Miller
3α-5α-Tetrahydroprogesterone, a progesterone metabolite also known as allopregnanolone, and 5α-androstane-3α,17β-diol, a testosterone metabolite also known as 3α-androstanediol, are neuroactive steroids and positive GABAA receptor allosteric modulators. Both anorexia nervosa (AN) and obesity are complicated by affective co-morbidities and hypothalamic-pituitary-gonadal dysregulation. However, it is not known whether neuroactive steroid levels are abnormal at the extremes of the weight spectrum. We hypothesized that serum allopregnanolone and 3α-androstanediol levels would be decreased in AN compared to healthy controls (HC) and negatively associated with affective symptoms throughout the weight spectrum, independent of body mass index (BMI)...
November 1, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29072794/effects-of-gaba-active-steroids-in-the-female-brain-with-focus-on-the-premenstrual-dysphoric-disorder
#5
REVIEW
Marie Bixo, Maja Johansson, Erika Timby, Louise Michalski, Torbjörn Bäckström
PMDD (premenstrual dysphoric disorder) afflicts 3-5% of women of childbearing age, and is characterized by recurrent negative mood symptoms, e.g. irritability, depression, anxiety and emotional lability during the luteal phase of the menstrual cycle. The etiology of PMDD is unknown, but a temporal association with circulating ovarian steroids, in particular progesterone and its metabolite allopregnanolone, during the luteal phase has been established. Allopregnanolone is a positive modulator of the GABAA receptor: it is sedative in high concentrations, but may precipitate paradoxical adverse effects on mood at levels corresponding to luteal phase concentrations in susceptible women...
October 26, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/29059599/a-comparison-of-progesterone-assays-for-determination-of-peripheral-pregnane-concentrations-in-the-late-pregnant-mare
#6
Michelle A A Wynn, Alejandro Esteller-Vico, Erin L Legacki, Alan J Conley, Shavahn C Loux, Scott D Stanley, Thomas E Curry, Edward L Squires, Mats H Troedsson, Barry A Ball
During the latter half of gestation in mares, there is a complex milieu of pregnanes in peripheral blood. Progesterone concentrations are often assessed by immunoassay during late gestation as a measure of pregnancy well-being; however, interpretation of results is complicated by the numerous cross-reacting pregnanes present in high concentrations during late gestation. Further, many mares are supplemented with an exogenous progestin, altrenogest, which may also cross-react with existing assays and further confound interpretation...
October 7, 2017: Theriogenology
https://www.readbyqxmd.com/read/29045302/neurosteroid-levels-in-patients-with-bipolar-disorder-and-a-history-of-cannabis-use-disorders
#7
Brittany L Mason, Erin Van Enkevort, Francesca Filbey, Christine E Marx, John Park, Alyson Nakamura, Prabha Sunderajan, E Sherwood Brown
PURPOSE/BACKGROUND: In animal models, levels of the neurosteroid pregnenolone increase after tetrahydrocannabinol (THC) administration and pregnenolone appears to attenuate the brain effects of THC. Given these interactions between pregnenolone and THC, we evaluated baseline neurosteroid levels in participants with a history of a cannabis use disorders (CUDs). METHODS/PROCEDURES: Bipolar depressed participants were enrolled in a randomized placebo-controlled clinical trial to evaluate the efficacy of add-on pregnenolone for depression and before receiving pregnenolone or placebo...
December 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28969480/maternal-stress-in-pregnancy-affects-myelination-and-neurosteroid-regulatory-pathways-in-the-guinea-pig-cerebellum
#8
Greer A Bennett, Hannah K Palliser, Julia C Shaw, Kerrin L Palazzi, David W Walker, Jonathan J Hirst
Prenatal stress predisposes offspring to behavioral pathologies. These may be attributed to effects on cerebellar neurosteroids and GABAergic inhibitory signaling, which can be linked to hyperactivity disorders. The aims were to determine the effect of prenatal stress on markers of cerebellar development, a key enzyme in neurosteroid synthesis and the expression of GABAA receptor (GABAAR) subunits involved in neurosteroid signaling. We used a model of prenatal stress (strobe light exposure, 2 h on gestational day 50, 55, 60 and 65) in guinea pigs, in which we have characterized anxiety and neophobic behavioral outcomes...
October 2, 2017: Stress: the International Journal on the Biology of Stress
https://www.readbyqxmd.com/read/28951257/protective-effects-of-the-neurosteroid-allopregnanolone-in-a-mouse-model-of-spontaneous-motoneuron-degeneration
#9
Maria Meyer, Laura I Garay, María Sol Kruse, Agustina Lara, Gisella Gargiulo-Monachelli, Michael Schumacher, Rachida Guennoun, Hector Coirini, Alejandro F De Nicola, Maria Claudia Gonzalez Deniselle
Amyotrophic lateral sclerosis (ALS) is a devastating disorder characterized by progressive death of motoneurons. The Wobbler (WR) mouse is a preclinical model sharing neuropathological similarities with human ALS. We have shown that progesterone (PROG) prevents the progression of motoneuron degeneration. We now studied if allopregnanolone (ALLO), a reduced metabolite of PROG endowed with gabaergic activity, also prevents WR neuropathology. Sixty-day old WRs remained untreated or received two steroid treatment regimens in order to evaluate the response of several parameters during early or prolonged steroid administration...
November 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28947177/resveratrol-ameliorated-the-behavioral-deficits-in-a-mouse-model-of-post-traumatic-stress-disorder
#10
Ze-Shun Zhang, Zhi-Kun Qiu, Jia-Li He, Xu Liu, Ji-Sheng Chen, Yu-Lu Wang
Post-traumatic stress disorder (PTSD) has become a major psychiatric and neurological issue. Resveratrol is shown to be effective on depression and anxiety. However, the mechanism of anti-PTSD-like effects of resveratrol remains unknown. The present study aimed to explore the possible molecular and cellular mechanisms underlying the anti-PTSD-like effects of resveratrol. Following a 2-day exposure to inescapable electric foot shocks, animals were administered resveratrol (10, 20, and 40mg/kg, i.g.) during the behavioral tests, which included contextual freezing measurement, elevated plus maze test, staircase test, and open field test...
October 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28905487/endogenous-neurosteroids-influence-synaptic-gabaa-receptors-during-post-natal-development
#11
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
#12
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
#13
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
#14
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
#15
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...
November 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
#16
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
#17
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
#18
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
#19
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
#20
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
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