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https://www.readbyqxmd.com/read/28334947/protocadherin-19-pcdh19-interacts-with-paraspeckle-protein-nono-to-co-regulate-gene-expression-with-estrogen-receptor-alpha-er%C3%AE
#1
Duyen H Pham, Chuan Tan, Claire C Homan, Kristy Kolc, Mark Corbett, Dale McAninch, Archa Fox, Paul Thomas, Raman Kumar, Jozef Gecz
De novo and inherited mutations of X-chromosome cell adhesion molecule protocadherin 19 (PCDH19) cause frequent, highly variable epilepsy, autism, cognitive decline and behavioural problems syndrome. Intriguingly, hemizygous null males are not affected while heterozygous females are, contradicting established X-chromosome inheritance. The disease mechanism is not known. Cellular mosaicism is the likely driver. We have identified p54nrb/NONO, a multifunctional nuclear paraspeckle protein with known roles in nuclear hormone receptor gene regulation, as a PCDH19 protein interacting partner...
March 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28318987/a-clinical-evaluation-of-the-pharmacokinetics-and-pharmacodynamics-of-intravenous-alfaxalone-in-cyclodextrin-in-male-and-female-rats-following-a-loading-dose-and-constant-rate-infusion
#2
Kate L White, Stuart Paine, John Harris
OBJECTIVE: To characterise, as a clinical study, the pharmacokinetics and pharmacodynamics and describe the hypnotic effect of the neurosteroid alfaxalone (3α-hydroxy-5 α-pregnane-11, 20-dione) formulated with 2-hydroxypropyl-β-cyclodextrin in male and female rats. STUDY DESIGN: Prospective, experimental laboratory study. ANIMALS: A total of 12 (six male and six female) adult, aged-matched Sprague Dawley rats. METHODS: Surgery and instrumentation was performed under isoflurane anaesthesia in an oxygen/nitrous oxide mixture (1:2) and local anaesthetic infiltration...
February 1, 2017: Veterinary Anaesthesia and Analgesia
https://www.readbyqxmd.com/read/28315270/sigma-1-receptor-agonists-and-their-clinical-implications-in-neuropsychiatric-disorders
#3
Yakup Albayrak, Kenji Hashimoto
Accumulating evidence suggests that sigma-1 receptors play a role in the pathophysiology of neuropsychiatric diseases, as well as in the mechanisms of some selective serotonin reuptake inhibitors (SSRIs). Among the SSRIs, the order of affinity for sigma-1 receptors is as follows: fluvoxamine > sertraline > fluoxetine > escitalopram > citalopram > paroxetine. Some SSRIs (e.g., fluvoxamine, fluoxetine and escitalopram) and other drugs (donepezil , ifenprodil , dehydroepiandeterone (DHEA)) potentiate nerve-growth factor (NGF)-induced neurite outgrowth in PC12 cells, and these effects could be antagonized by the selective sigma-1 receptor antagonist NE-100...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28295708/seasonal-alterations-in-the-daily-rhythms-in-hypothalamic-expression-of-genes-involved-in-the-photoperiodic-transduction-and-neurosteroid-dependent-processes-in-migratory-blackheaded-buntings
#4
Ila Mishra, Devraj Singh, Vinod Kumar
This study investigated seasonal alterations in the daily rhythms of hypothalamic expression of genes involved in the photoperiodic regulation of annual cycles in birds. We measured 4-hourly mRNA expression of genes involved in the photoperiodic transduction (OPN5, EYA3, CGA, TSHβ, DIO2, DIO3) and neurosteroid-dependent processes (AR, CYP19, ERα, ERβ) in the hypothalamus of migratory blackheaded buntings photoinduced with photosensitive, photostimulated (early and late stimulated) and photorefractory seasonal states...
March 14, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28280460/androstenediol-reduces-demyelination-induced-axonopathy-in-the-rat-corpus-callosum-impact-on-microglial-polarization
#5
Samah Kalakh, Abdeslam Mouihate
Aims: We have previously shown that the neurosteroid androstenediol (ADIOL) promotes remyelination following gliotoxin-induced demyelination. However, the impact of this ADIOL on axonal recovery is not yet known. In the present study, we investigated the impact of ADIOL on axonal integrity following a focal demyelination in the corpus callosum. Methods: A 2 μl solution of either ethidium bromide (EB; 0.04%) or pyrogen-free saline were stereotaxically injected into the corpus callosum of Sprague Dawley rats...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28274826/the-novel-dehydroepiandrosterone-dhea-derivative-bnn27-counteracts-delay-dependent-and-scopolamine-induced-recognition-memory-deficitsm-in-rats
#6
Nikolaos Pitsikas, Achille Gravanis
Experimental evidence indicates that the neurosteroids dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) are involved in cognition. BNN27 is a novel 17C spiroepoxy-DHEA derivative, which devoid of steroidogenic activity. The neuroprotective effects of BNN27 have been recently reported. The present study was designed to investigate the effects of BNN27 on recognition memory in rats. For this purpose, the novel object task (NOT), a procedure assessing non-spatial recognition memory and the novel location task (NLT), a procedure evaluating spatial recognition memory were used...
March 6, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28245513/brain-translocator-protein-occupancy-by-ono-2952-in-healthy-adults-a-phase-1-pet-study-using-11-c-pbr28
#7
William G Frankle, Rajesh Narendran, Andrew T Wood, Fumitaka Suto, Michael L Himes, Michiyoshi Kobayashi, Tomoya Ohno, Akinori Yamauchi, Katsukuni Mitsui, Kevin Duffy, Bruce Mark
ONO-2952, a novel antagonist of translocator protein 18 kDa (TSPO), binds with high affinity to TSPO in rat brain and human tumor cell line membrane preparations. This study used the TSPO-specific PET radioligand [(11) C]PBR28 to confirm binding of ONO-2952 to brain TSPO in human subjects, and evaluate brain TSPO occupancy and its relationship with ONO-2952 plasma concentration. Sixteen healthy subjects received a single oral dose of 200, 60, 20, or 6 mg ONO-2952 (n=4 per dose). Two PET scans with [(11) C]PBR28 were conducted ≤7 days apart: at baseline and 24 hours after ONO-2952 administration...
February 28, 2017: Synapse
https://www.readbyqxmd.com/read/28236431/catamenial-like-seizure-exacerbation-in-mice-with-targeted-ablation-of-extrasynaptic-%C3%AE-gaba-a-receptors-in-the-brain
#8
Bryan L Clossen, Doodipala Samba Reddy
Neurosteroids play a key role in catamenial epilepsy, a menstrual cycle-related seizure clustering in women with epilepsy. While neurosteroids act on all GABA-A receptor isoforms, they cause greater effects on extrasynaptic δGABA-A receptors that mediate tonic inhibition in the brain. Previously, we identified a potential GABA-A receptor mechanism for catamenial epilepsy. However, the precise functional role of extrasynaptic δGABA-A receptors in the pathophysiology of catamenial epilepsy remains unclear. In this study, we utilized mice lacking extrasynaptic δGABA-A receptors (δKO) to investigate whether reduction of tonic inhibition affects catamenial seizure susceptibility or intensity...
February 25, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28220044/pregnenolone-blocks-cannabinoid-induced-acute-psychotic-like-states-in-mice
#9
A Busquets-Garcia, E Soria-Gómez, B Redon, Y Mackenbach, M Vallée, F Chaouloff, M Varilh, G Ferreira, P-V Piazza, G Marsicano
Cannabis-induced acute psychotic-like states (CIAPS) represent a growing health issue, but their underlying neurobiological mechanisms are poorly understood. The use of antipsychotics and benzodiazepines against CIAPS is limited by side effects and/or by their ability to tackle only certain aspects of psychosis. Thus, safer wide-spectrum treatments are currently needed. Although the blockade of cannabinoid type-1 receptor (CB1) had been suggested as a therapeutical means against CIAPS, the use of orthosteric CB1 receptor full antagonists is strongly limited by undesired side effects and low efficacy...
February 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28217829/vitamin-d-and-autism-what-s-new
#10
REVIEW
John Jacob Cannell
An increasing amount of evidence points to the possibility that gestational and early childhood vitamin D deficiency [25(OH)D < 40 ng/ml] cause some cases of autism. Vitamin D is metabolized into a seco-steroid hormone that regulates about 3% of the 26,000 genes in the coding human genome. It is also a neurosteroid that is active in brain development, having effects on cellular proliferation, differentiation, calcium signaling, neurotrophic and neuroprotective actions; it also appears to have an effect on neurotransmission and synaptic plasticity...
February 20, 2017: Reviews in Endocrine & Metabolic Disorders
https://www.readbyqxmd.com/read/28207286/lc-ms-ms-simultaneous-analysis-of-allopregnanolone-epiallopregnanolone-pregnanolone-dehydroepiandrosterone-and-dehydroepiandrosterone-3-sulfate-in-human-plasma
#11
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...
March 2017: Bioanalysis
https://www.readbyqxmd.com/read/28202290/effect-of-psychotropic-drug-treatment-on-sterol-metabolism
#12
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
#13
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 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28192175/increased-anxiety-like-phenotype-in-female-guinea-pigs-following-reduced-neurosteroid-exposure-in-utero
#14
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...
May 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28179120/novel-therapeutic-approaches-for-disease-modification-of-epileptogenesis-for-curing-epilepsy
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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