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https://www.readbyqxmd.com/read/28207286/lc-ms-ms-simultaneous-analysis-of-allopregnanolone-epiallopregnanolone-pregnanolone-dehydroepiandrosterone-and-dehydroepiandrosterone-3-sulfate-in-human-plasma
#1
Luana Lionetto, Fernando De Andrés, Matilde Capi, Martina Curto, Donata Sabato, Maurizio Simmaco, Paola Bossù, Eleonora Sacchinelli, Maria Donata Orfei, Federica Piras, Nerisa Banaj, Gianfranco Spalletta
AIM: Several neuropsychopharmacological properties have been attributed to the 3α-reduced pregnane steroids, allopregnanolone and pregnanolone, as well as to dehydroepiandrosterone sulfate because of their ability to modulate γ-aminobutyric acid (GABAA) receptors in the CNS. In order to understand better their role in several mechanisms in CNS, a new methodology is proposed to monitor these compounds in human plasma. Methodology & results: The analytes were first derivatized with 2-hydrazinopyridine and extracted from plasma using SPE...
February 16, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28202290/effect-of-psychotropic-drug-treatment-on-sterol-metabolism
#2
Željka Korade, Wei Liu, Emily B Warren, Kristan Armstrong, Ned A Porter, Christine Konradi
Cholesterol metabolism is vital for brain function. Previous work in cultured cells has shown that a number of psychotropic drugs inhibit the activity of 7-dehydrocholesterol reductase (DHCR7), an enzyme that catalyzes the final steps in cholesterol biosynthesis. This leads to the accumulation of 7-dehydrocholesterol (7DHC), a molecule that gives rise to oxysterols, vitamin D, and atypical neurosteroids. We examined levels of cholesterol and the cholesterol precursors desmosterol, lanosterol, 7DHC and its isomer 8-dehydrocholesterol (8DHC), in blood samples of 123 psychiatric patients on various antipsychotic and antidepressant drugs, and 85 healthy controls, to see if the observations in cell lines hold true for patients as well...
February 12, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28194953/click-chemistry-reagent-for-identification-of-sites-of-covalent-ligand-incorporation-in-integral-membrane-proteins
#3
Melissa M Budelier, Wayland W L Cheng, Lucie Bergdoll, Zi-Wei Chen, Jeff Abramson, Kathiresan Krishnan, Mingxing Qian, Douglas F Covey, James W Janetka, Alex S Evers
Identifying sites of protein-ligand interaction is important for structure-based drug discovery and understanding protein structure-function relationships. Mass spectrometry (MS) has emerged as a useful tool for identifying residues covalently modified by ligands. Current methods use database searches that are dependent on acquiring interpretable fragmentation spectra (MS2) of peptide-ligand adducts. This is problematic for identifying sites of hydrophobic ligand incorporation in integral membrane proteins (IMPs), where poor aqueous solubility and ionization of peptide-ligand adducts and collision-induced adduct loss hinder the acquisition of quality MS2 spectra...
February 9, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28192175/increased-anxiety-like-phenotype-in-female-guinea-pigs-following-reduced-neurosteroid-exposure-in-utero
#4
Angela L Cumberland, Hannah K Palliser, Gabrielle K Crombie, David W Walker, Jonathan J Hirst
Neurosteroids are essential for aiding proper fetal neurodevelopment. Pregnancy compromises such as preterm birth, prenatal stress and intrauterine growth restriction are associated with an increased risk of developing behavioural and mood disorders, particularly during adolescence. These pathologies involve the premature loss or alteration of trophic steroid hormones reaching the fetus leading to impaired neurodevelopment. While the specific programming mechanisms are yet to be fully elucidated, in adult life, dysfunctions of allopregnanolone action are prevalent in individuals with depression, post-traumatic stress disorder and anxiety disorders...
February 9, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28179120/novel-therapeutic-approaches-for-disease-modification-of-epileptogenesis-for-curing-epilepsy
#5
REVIEW
Bryan L Clossen, Doodipala Samba Reddy
This article describes the recent advances in epileptogenesis and novel therapeutic approaches for the prevention of epilepsy, with a special emphasis on the pharmacological basis of disease-modification of epileptogenesis for curing epilepsy. Here we assess animal studies and human clinical trials of epilepsy spanning 1982-2016. Epilepsy arises from a number of neuronal factors that trigger epileptogenesis, which is the process by which a brain shifts from a normal physiologic state to an epileptic condition...
February 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28162665/-419-neurosteroid-levels-are-inversely-associated-with-low-back-pain-in-female-iraq-afghanistan-era-veterans
#6
J Naylor, J Kilts, J Strauss, S Szabo, C Dunn, H Wagner, R Hamer, L Shampine, J Zanga, C Marx
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28146602/pharmacological-characterization-of-the-excitatory-cys-loop-gaba-receptor-family-in-c-elegans
#7
Georgina C B Nicholl, Ali K Jawad, Robert Weymouth, Haoming Zhang, Asim A Beg
BACKGROUND AND PURPOSE: Ionotropic GABA receptors are evolutionarily conserved proteins that mediate cellular and network inhibition in both vertebrates and invertebrates. A unique class of excitatory GABA receptors has been identified in several nematode species. Despite well-characterized functions in C. elegans, little is known about the pharmacology of the excitatory GABA receptors EXP-1 and LGC-35. Using a panel of compounds that differentially activate and modulate ionotropic GABA receptors, we investigated the agonist binding site and allosteric modulation of EXP-1 and LGC-35...
February 1, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28137424/pr-independent-neurosteroid-regulation-of-%C3%AE-2-gaba-a-receptors-mrna-in-the-hippocampus-subfields
#8
Doodipala Samba Reddy, Omkaram Gangisetty, Xin Wu
Progesterone (P) binding to the intracellular progesterone receptors (PRs) plays a key role in epilepsy via modulation of GABA-A receptor plasticity in the brain. This is thought to occur via conversion of P to neurosteroids such as allopregnanolone, an allosteric modulator of GABA-A receptors. In the female brain, the composition of GABA-A receptors is not static and undergoes dynamic spatial changes in response to fluctuations in P and neurosteroid levels. Synaptic α2-containing GABA-A receptors contribute to phasic neuronal excitability and seizure susceptibility...
January 27, 2017: Brain Research
https://www.readbyqxmd.com/read/28131725/the-5-alpha-reductase-inhibitor-finasteride-reduces-dyskinesia-in-a-rat-model-of-parkinson-s-disease
#9
Roberto Frau, Paola Savoia, Silvia Fanni, Chiara Fiorentini, Camino Fidalgo, Elisabetta Tronci, Roberto Stancampiano, Mario Meloni, Antonino Cannas, Francesco Marrosu, Marco Bortolato, Paola Devoto, Cristina Missale, Manolo Carta
Levodopa-induced dyskinesia (LID) is a disabling motor complication occurring in Parkinson's disease patients (PD) after long-term l-DOPA treatment. Although its etiology remains unclear, there is accumulating evidence that LID relies on an excessive dopamine receptor transmission, particularly at the downstream signaling of D1 receptors. We previously reported that the pharmacological blockade of 5-alpha reductase (5AR), the rate limiting enzyme in neurosteroids synthesis, rescued a number of behavioral aberrations induced by D1 receptor-selective and non-selective agonists, without inducing extrapyramidal symptoms...
January 26, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28129443/anxiolytic-effects-of-hippocampal-neurosteroids-in-normal-and-neuropathic-rats-with-spared-nerve-injury
#10
Meng Zhang, Jia Liu, Meng-Meng Zhou, Honghai Wu, Yanning Hou, Yun-Feng Li, Yuxin Yin, Lemin Zheng, Jie Cai, Fei-Fei Liao, Feng-Yu Liu, Ming Yi, You Wan
Neurosteroids are synthesized in the nervous system from cholesterol or steroidal precursors imported from peripheral sources. These compounds are important allosteric modulators of GABAA receptors, which play a vital role in modulating hippocampal functions. Chronic pain is accompanied by increased neurosteroid production in the spinal cord and thalamus. We hypothesize that hippocampal neurosteroids participate in pain or pain-associated emotions, which we tested with high-performance liquid chromatography/tandem mass spectrometry and pharmacological behavioral tests...
January 27, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28102853/skin-to-skin-contact-after-birth-and-the-natural-course-of-neurosteroid-levels-in-healthy-term-newborns
#11
K R McCallie, N W Gaikwad, M E Castillo Cuadrado, M Aleman, J E Madigan, D K Stevenson, V K Bhutani
OBJECTIVE: To determine the postnatal course of neurosteroid levels in relation to gender, mode of delivery and the extent of skin-to-skin (STS) contact during the first days of life in healthy term newborns. STUDY DESIGN: Prospective observational study of 39 neonates in which parents recorded total duration of STS in the first 2 days and nine neurosteroids (dehydroepiandrosterone-sulfate, progesterone, pregnenolone, pregnenolone-sulfate, allopregnanolone, isopregnanolone, epipregnanolone, pregnanolone and pregnanolone-sulfate) were assayed from blood samples at birth and at 1-2 days of age...
January 19, 2017: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/28102229/the-neurosteroidogenic-enzyme-5%C3%AE-reductase-mediates-psychotic-like-complications-of-sleep-deprivation
#12
Roberto Frau, Valentina Bini, Alessio Soggiu, Simona Scheggi, Alessandra Pardu, Silvia Fanni, Paola Roncada, Monica Puligheddu, Francesco Marrosu, Donatella Caruso, Paola Devoto, Marco Bortolato
Acute sleep deprivation (SD) can trigger or exacerbate psychosis- and mania-related symptoms; the neurobiological basis of these complications, however, remains elusive. Given the extensive involvement of neuroactive steroids in psychopathology, we hypothesized that the behavioral complications of SD may be contributed by 5α-reductase (5αR), the rate-limiting enzyme in the conversion of progesterone into the neurosteroid allopregnanolone. We first tested whether rats exposed to SD may exhibit brain-regional alterations in 5αR isoenzymes and neuroactive steroid levels; then, we assessed whether the behavioral and neuroendocrine alterations induced by SD may be differentially modulated by the administration of the 5αR inhibitor finasteride, as well as progesterone and allopregnanolone...
January 19, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28077388/the-na-taurocholate-cotransporting-polypeptide-ntcp-slc10a1-ortholog-in-the-marine-skate-leucoraja-erinacea-is-not-a-physiological-bile-salt-transporter
#13
Dongke Yu, Han Zhang, Daniel A Lionarons, James L Boyer, Shi-Ying Cai
The Na(+)-dependent taurocholate co-transporting polypeptide (NTCP/SLC10A1) is a hepatocyte specific solute carrier, which plays an important role in maintaining bile salt homeostasis in mammals. The absence of an hepatic Na(+)-dependent bile salt transport system in marine skate and rainbow trout raises a question regarding the function of the Slc10a1 gene in these species. Here we have characterized the Slc10a1 gene in the marine skate, Leucoraja erinacea. The transcript of skate Slc10a1 (skSlc10a1) encodes 319 amino acids and shares 46% identity to human NTCP (hNTCP) with similar topology to mammalian NTCP...
January 11, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28043845/distributions-of-therapeutically-promising-neurosteroids-in-cellular-membranes
#14
Kamila Riedlová, Michaela Nekardová, Petr Kačer, Kamila Syslová, Mario Vazdar, Pavel Jungwirth, Eva Kudová, Lukasz Cwiklik
Interactions of two neurosteroids, inhibiting membrane-bound N-Methyl-d-aspartate receptors, with phospholipid membranes are studied. Namely, endogenous pregnanolone sulfate is compared with pregnanolone glutamate, the latter being a novel synthetic steroidal inhibitor of these receptors with potential pharmaceutical use. Molecular-level details of steroid-phospholipid membranes interactions are scrutinized employing molecular dynamics simulations supported by quantum chemical calculations to assess steroid lipophilicity...
December 30, 2016: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28038403/higher-serum-dhea-concentrations-before-and-after-ssri-treatment-are-associated-with-remission-of-major-depression
#15
Christina M Hough, Daniel Lindqvist, Elissa S Epel, Molly St Denis, Victor I Reus, F Saverio Bersani, Rebecca Rosser, Laura Mahan, Heather M Burke, Owen M Wolkowitz, Synthia H Mellon
BACKGROUND: Dehydroepiandrosterone (DHEA) and its sulfated ester DHEA-sulfate (DHEA-S), (together DHEA[S]), are the most abundant adrenal steroids in humans and are found in blood and the brain, where they function as neurosteroids with direct receptor affinities. Preclinical studies suggest that DHEA(S) has antidepressant/neuroprotective properties, and exogenously administered DHEA has shown antidepressant efficacy in humans. Nonetheless, the role of endogenous DHEA(S) levels in major depressive disorder (MDD) and antidepressant outcomes remains unclear...
December 5, 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28028198/sex-dependent-regulation-of-aromatase-mediated-synaptic-plasticity-in-the-basolateral-amygdala
#16
Roland A Bender, Lepu Zhou, Ricardo Vierk, Nicola Brandt, Alexander Keller, Christine E Gee, Michael K E Schäfer, Gabriele M Rune
The basolateral amygdala (BLA) integrates sensory input from cortical and subcortical regions, a function that requires marked synaptic plasticity. Here we provide evidence that cytochrome P450 aromatase (AROM), the enzyme converting testosterone to 17β-estradiol (E2), contributes to the regulation of this plasticity in a sex-specific manner. We show that AROM is expressed in the BLA, particularly in the basolateral nucleus (BL), in male and female rodents. Systemic administration of the AROM inhibitor letrozole reduced spine synapse density in the BL of adult female mice but not in the BL of male mice...
February 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28027915/developmental-vitamin-d-deficiency-and-autism-putative-pathogenic-mechanisms
#17
REVIEW
Asad Ali, Xiaoying Cui, Darryl Eyles
Autism is a neurodevelopmental disease that presents in early life. Despite a considerable amount of studies, the neurobiological mechanisms underlying autism remain obscure. Both genetic and environmental factors are involved in the development of autism. Vitamin D deficiency is emerging as a consistently reported risk factor in children. One reason for the prominence now being given to this risk factor is that it would appear to interact with several other epidemiological risk factors for autism. Vitamin D is an active neurosteroid and plays crucial neuroprotective roles in the developing brain...
December 24, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28027903/seasonal-changes-and-sexual-dimorphism-in-gene-expression-of-star-protein-steroidogenic-enzymes-and-sex-hormone-receptors-in-the-frog-brain
#18
Alessandra Santillo, Sara Falvo, Maria Maddalena Di Fiore, Gabriella Chieffi Baccari
The brain of amphibians contains all the key enzymes of steroidogenesis and has a high steroidogenic activity. In seasonally-breeding amphibian species brain steroid levels fluctuate synchronously with the reproductive cycle. Here we report a study of gene expression of StAR protein, key steroidogenic enzymes and sex hormone receptors in the telencephalon (T) and diencephalon-mesencephalon (D-M) of male and female reproductive and post-reproductive Pelophylax esculentus, a seasonally breeding anuran amphibian...
December 24, 2016: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28009705/positive-allosteric-modulation-of-gabaa-receptors-attenuates-high-blood-pressure-in-schlager-hypertensive-mice
#19
Emily R Stevenson, Esther M C Johns, Francine Z Marques, Kristy L Jackson, Pamela J Davern, Roger G Evans, Geoffrey A Head
OBJECTIVE: Blood pressure high Schlager (BPH/2J) mice have neurogenic hypertension associated with differences in hypothalamic GABAA receptors compared with their normotensive counterparts (BPN/3J). Allopregnanolone is an endogenous neurosteroid reduced in chronic stress, and when administered, decreases anxiety by positive allosteric modulation of GABAA receptors. METHODS: To determine if allopregnanolone could be a viable therapeutic for neurogenic hypertension, male BPH/2J (n = 6-7) and BPN/3J (n = 8-9) mice were equipped with radiotelemetry probes to compare cardiovascular variables before and after implantation of subcutaneous minipumps delivering allopregnanolone (5 mg/kg per day), or its vehicle, for a period of 2 weeks...
March 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28005271/progesterone-for-acute-traumatic-brain-injury
#20
REVIEW
Junpeng Ma, Siqing Huang, Shu Qin, Chao You, Yunhui Zeng
BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability, and the identification of effective, inexpensive and widely practicable treatments for brain injury is of great public health importance worldwide. Progesterone is a naturally produced hormone that has well-defined pharmacokinetics, is widely available, inexpensive, and has steroidal, neuroactive and neurosteroidal actions in the central nervous system. It is, therefore, a potential candidate for treating TBI patients...
22, 2016: Cochrane Database of Systematic Reviews
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