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https://www.readbyqxmd.com/read/29777410/startling-differences-using-the-acoustic-startle-response-to-study-sex-differences-and-neurosteroids-in-affective-disorders
#1
REVIEW
Liisa Hantsoo, Carla E M Golden, Sara Kornfield, Christian Grillon, C Neill Epperson
PURPOSE OF REVIEW: Neuroactive steroid hormones, such as estradiol and progesterone, likely play a role in the pathophysiology of female-specific psychiatric disorders such as premenstrual dysphoric disorder (PMDD) and postpartum depression and may contribute to the marked sex differences observed in the incidence and presentation of affective disorders. However, few tools are available to study the precise contributions of these neuroactive steroids (NSs). In this review, we propose that the acoustic startle response (ASR), an objective measure of an organism's response to an emotional context or stressor, is sensitive to NSs...
May 18, 2018: Current Psychiatry Reports
https://www.readbyqxmd.com/read/29777319/what-does-sex-have-to-do-with-it-the-role-of-sex-as-a-biological-variable-in-the-development-of-posttraumatic-stress-disorder
#2
REVIEW
Sara L Kornfield, Liisa Hantsoo, C Neill Epperson
PURPOSE OF REVIEW: This review highlights the neurobiological aspects of sex differences in posttraumatic stress disorder (PTSD), specifically focusing on the physiological responses to trauma and presents evidence supporting hormone and neurosteroid/peptide differences from both preclinical and clinical research. RECENT FINDINGS: While others have suggested that trauma type or acute emotional reaction are responsible for women's disproportionate risk to PTSD, neither of these explanations fully accounts for the sex differences in PTSD...
May 18, 2018: Current Psychiatry Reports
https://www.readbyqxmd.com/read/29773855/the-anxiolytic-like-effects-of-ginsenoside-rg3-on-chronic-unpredictable-stress-in-rats
#3
Jia-Ning Xu, Li-Fang Chen, Jun Su, Zhi-Li Liu, Jie Chen, Qing-Fen Lin, Wei-Dong Mao, Dong Shen
The present study is to evaluate the anxiolytic-like activities underlying ginsenoside Rg3 (GRg3). The anxiolytic-like activities were induced by GRg3 (20 and 40 mg/kg, i.g), evidenced by blocking the decreased time and entries in the open arms in elevated plus maze test and by reversing the increased latency to feed in novelty-suppressed feeding test. In addition, the decreased levels on progesterone, allopregnanolone, serotonin (5-HT) in the prefrontal cortex and hippocampus of chronic unpredictable stress (CUS) were blocked by GRg3 (20 and 40 mg/kg, i...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773519/the-neurosteroid-allopregnanolone-sulfate-inhibits-na-v-1-3-%C3%AE-subunit-containing-voltage-gated-sodium-channels-expressed-in-xenopus-oocytes
#4
Takafumi Horishita, Nobuyuki Yanagihara, Susumu Ueno, Dan Okura, Reiko Horishita, Tomoko Minami, Yuichi Ogata, Yuka Sudo, Yasuhito Uezono, Takashi Kawasaki
The neurosteroid allopregnanolone has potent analgesic effects, and its potential use for neuropathic pain is supported by recent reports. However, the analgesic mechanisms are obscure. The voltage-gated sodium channels (Nav ) α subunit Nav 1.3 is thought to play an essential role in neuropathic pain. Here, we report the effects of allopregnanolone sulfate (APAS) on sodium currents (INa ) in Xenopus oocytes expressing Nav 1.3 with β1 or β3 subunits. APAS suppressed INa of Nav 1.3 with β1 and β3 in a concentration-dependent manner (IC50 values; 75 and 26 μmol/L)...
March 30, 2018: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29763637/neurosteroid-pregnenolone-sulfate-alone-and-as-augmentation-of-lurasidone-or-tandospirone-rescues-phencyclidine-induced-deficits-in-cognitive-function-and-social-interaction
#5
L Rajagopal, D Soni, H Y Meltzer
BACKGROUND: Pregnenolone sulfate (PregS), an endogenous neurosteroid, which negatively and positively modulates gamma amino butyric acid subunit A (GABAA ) and N-methyl D-aspartate (NMDA) receptors (R) respectively, among other potential neuroplastic changes on synaptic processes, has shown some beneficial effects on treating cognitive impairment associated with schizophrenia (CIAS) and negative symptoms. Lurasidone (Lur), an atypical antipsychotic drug (AAPD), and tandospirone (Tan), a 5-HT1A  R partial agonist, have also been reported to improve cognitive or negative symptoms, or both, in some schizophrenia patients...
May 12, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29751108/basal-glucocorticoid-receptor-activation-induces-proliferation-and-inhibits-neuronal-differentiation-of-human-induced-pluripotent-stem-cell-derived-neuronal-precursor-cells
#6
Elina Nürnberg, Sandra Horschitz, Patrick Schloss, Andreas Meyer-Lindenberg
Glucocorticoids (GC) have first been shown to originate from the adrenal glands where synthesis and release is controlled by the hypothalamic-pituitary-adrenal (HPA) axis. Recently, it was shown that GC and other steroid hormones are also synthesized in the central nervous system, so-called neurosteroids. GC bind to specific GC receptors (GR) which function as ligand-activated transcription factors. GR are expressed in nearly all cell types in the brain, and therefore GC have a strong impact on neuronal development...
May 8, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29740398/neurosteroids-in-adult-hippocampus-of-male-and-female-rodents-biosynthesis-and-actions-of-sex-steroids
#7
REVIEW
Yasushi Hojo, Suguru Kawato
The brain is not only the target of steroid hormones but also is able to locally synthesize steroids de novo . Evidence of the local production of steroids in the brain has been accumulating in various vertebrates, including teleost fish, amphibia, birds, rodents, non-human primates, and humans. In this review, we mainly focus on the local production of sex steroids in the hippocampal neurons of adult rodents (rats and mice), a center for learning and memory. From the data of the hippocampus of adult male rats, hippocampal principal neurons [pyramidal cells in CA1-CA3 and granule cells in dentate gyrus (DG)] have a complete system for biosynthesis of sex steroids...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29729249/neurosteroid-allopregnanolone-reduces-ipsilateral-visual-cortex-potentiation-following-unilateral-optic-nerve-injury
#8
Elena G Sergeeva, Claudia Espinosa-Garcia, Fahim Atif, Machelle T Pardue, Donald G Stein
In adult mice with unilateral optic nerve crush injury (ONC), we studied visual response plasticity in the visual cortex following stimulation with sinusoidal grating. We examined visually evoked potentials (VEP) in the primary visual cortex ipsilateral and contralateral to the crushed nerve. We found that unilateral ONC induces enhancement of visual response on the side ipsilateral to the injury that is evoked by visual stimulation to the intact eye. This enhancement was associated with supranormal spatial frequency thresholds in the intact eye when tested using optomotor response...
May 2, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29728813/the-dynamics-of-neurosteroids-and-sex-related-hormones-in-the-pathogenesis-of-alzheimer-s-disease
#9
REVIEW
Milad Hasanpour, Alireza Nourazarian, Mohammad Hossein Geranmayeh, Masoud Nikanfar, Fatemeh Khaki-Khatibi, Reza Rahbarghazi
Alzheimer's disease (AD) is commonly diagnosed by vast extracellular amyloid deposits and existence of intracellular neurofibrillary tangles. In accordance with the literature, age-related loss of sex steroid hormones in either males or females was found in relation to AD subjects. The dynamics of these hormones have been previously described in both physiological and pathological conditions with the evidence of changes in various intracellular signalings regarding the neurodegenerative disease. The potent protective effects of sex steroid hormones and their synthetic analogs are indicative of the decrease in the accumulated levels of intercellular beta-amyloid (Aβ) protein and an increase of specific proteases activity, resulting in the improvement of pathological features...
May 4, 2018: Neuromolecular Medicine
https://www.readbyqxmd.com/read/29727810/ptsd-in-women-is-associated-with-a-block-in-conversion-of-progesterone-to-the-gabaergic-neurosteroids-allopregnanolone-and-pregnanolone-measured-in-plasma
#10
S L Pineles, Y I Nillni, G Pinna, J Irvine, A Webb, K A Arditte Hall, R Hauger, M W Miller, P A Resick, S P Orr, A M Rasmusson
There is a need to identify new and more effective treatments for posttraumatic stress disorder (PTSD). Allopregnanolone and its stereoisomer pregnanolone (together termed ALLO) are metabolites of progesterone that positively and allosterically modulate GABA effects at GABAA receptors, thereby reducing anxiety and depression. Previous research revealed that women with PTSD had low cerebrospinal fluid (CSF) ALLO levels and a low ratio of ALLO to the allopregnanolone precursor 5α-DHP, consistent with deficient activity of the ALLO synthetic enzyme 3α-hydroxysteroid dehydrogenase (3α-HSD)...
April 24, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29705269/structure-and-dynamics-of-neurosteroid-binding-to-the-%C3%AE-1-%C3%AE-2-%C3%AE-2-gaba-a-receptor
#11
Lautaro D Alvarez, Adali Pecci
Neurosteroids are the principal endogenous modulators of the γ-Aminobutyric acid receptors (GABAA Rs), pentameric membrane-bound proteins that can be assembled from at least 19 subunits. In the most abundant GABAA R arrangement (α1 β2 γ2 ), neurosteroids can potentiate the GABA action as well as produce a direct activation of the channel. The recent crystal structures of neurosteroids bound to α homopentameric GABAA R reveal binding to five equivalent sites. However, these results have been obtained using receptors that are not physiologically relevant, suggesting a need to investigate neurosteroid binding to heteropentameric receptors that exist in the central nervous system...
April 26, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29699872/methods-in-endogenous-steroid-profiling-a-comparison-of-gas-chromatography-mass-spectrometry-gc-ms-with-supercritical-fluid-chromatography-tandem-mass-spectrometry-sfc-ms-ms
#12
Juliane Teubel, Bernhard Wüst, Carola G Schipke, Oliver Peters, Maria Kristina Parr
In various fields of endocrinology, the determination of steroid hormones synthesised by the human body plays an important role. Research on central neurosteroids has been intensified within the last years, as they are discussed as biomarkers for various cognitive disorders. Their concentrations in cerebrospinal fluid (CSF) are considered to be regulated independently from peripheral fluids. For that reason, the challenging matrix CSF becomes a very interesting specimen for analysis. Concentrations are expected to be very low and available amount of CSF is limited...
April 17, 2018: Journal of Chromatography. A
https://www.readbyqxmd.com/read/29695968/neurosteroid-transport-in-the-brain-role-of-abc-and-slc-transporters
#13
REVIEW
Markus Grube, Paul Hagen, Gabriele Jedlitschky
Neurosteroids, comprising pregnane, androstane, and sulfated steroids can alter neuronal excitability through interaction with ligand-gated ion channels and other receptors and have therefore a therapeutic potential in several brain disorders. They can be formed in brain cells or are synthesized by an endocrine gland and reach the brain by penetrating the blood-brain barrier (BBB). Especially sulfated steroids such as pregnenolone sulfate (PregS) and dehydroepiandrosterone sulfate (DHEAS) depend on transporter proteins to cross membranes...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29681796/surface-expression-function-and-pharmacology-of-disease-associated-mutations-in-the-membrane-domain-of-the-human-glun2b-subunit
#14
Vojtech Vyklicky, Barbora Krausova, Jiri Cerny, Marek Ladislav, Tereza Smejkalova, Bohdan Kysilov, Miloslav Korinek, Sarka Danacikova, Martin Horak, Hana Chodounska, Eva Kudova, Ladislav Vyklicky
N-methyl-D-aspartate receptors (NMDARs), glutamate-gated ion channels, mediate signaling at the majority of excitatory synapses in the nervous system. Recent sequencing data for neurological and psychiatric patients have indicated numerous mutations in genes encoding for NMDAR subunits. Here, we present surface expression, functional, and pharmacological analysis of 11 de novo missense mutations of the human hGluN2B subunit (P553L; V558I; W607C; N615I; V618G; S628F; E657G; G820E; G820A; M824R; L825V) located in the pre-M1, M1, M2, M3, and M4 membrane regions...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29669258/rapid-effects-on-memory-consolidation-and-spine-morphology-by-estradiol-in-female-and-male-rodents
#15
REVIEW
Victoria Luine, Peter Serrano, Maya Frankfurt
Rapid, neurosteroid-like effects of estrogens on memory consolidation during recognition memory tasks in both male and female rodents are described. We discuss how these mnemonic changes are related to rapid estrogenic effects on dendritic spine density, the distribution of spine types and the expression of PSD95 and GluA2 within spines in the hippocampus and medial prefrontal cortex, two areas critical for learning and memory. Overall, these data lead to the conclusion that estrogens are capable of exerting rapid and potent influences on memory and spine morphology in both sexes...
April 15, 2018: Hormones and Behavior
https://www.readbyqxmd.com/read/29665500/aromatase-inhibition-by-letrozole-attenuates-kainic-acid-induced-seizures-but-not-neurotoxicity-in-mice
#16
Ramsha Iqbal, Gaurav K Jain, Fouzia Siraj, Divya Vohora
Evidence shows neurosteroids play a key role in regulating epileptogenesis. Neurosteroids such as testosterone modulate seizure susceptibility through its transformation to metabolites which show proconvulsant and anticonvulsant effects, respectively. Reduction of testosterone by aromatase generates proconvulsant 17-β estradiol. Alternatively, testosterone is metabolized into 5α-dihydrotestosterone (5α-DHT) by 5α-reductase, which is then reduced by 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR) to form anticonvulsant metabolite 3α-androstanediol (3α-Diol), a potent GABAA receptor modulating neurosteroid...
April 9, 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29622679/an-inter-subunit-electrostatic-interaction-in-the-gaba-a-receptor-facilitates-its-responses-to-benzodiazepines
#17
Natasha C Pflanz, Anna W Daszkowski, Garrett L Cornelison, James R Trudell, S John Mihic
Benzodiazepines are positive allosteric modulators of the GABAA receptor (GABAA R), acting at the α-γ subunit interface to enhance GABAA R function. GABA or benzodiazepine binding induces distinct conformational changes in the GABAA R. The molecular rearrangements in the GABAA R following benzodiazepine binding remain to be fully elucidated. Using two molecular models of the GABAA R, we identified electrostatic interactions between specific amino acids at the α-γ subunit interface which were broken by, or formed after, benzodiazepine binding...
April 5, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29602830/3%C3%AE-methyl-neurosteroid-analogs-are-preferential-positive-allosteric-modulators-and-direct-activators-of-extrasynaptic-%C3%AE-gaba-a-receptors-in-the-hippocampus-dentate-gyrus-subfield
#18
Shu-Hui Chuang, Doodipala Samba Reddy
Neurosteroids are powerful modulators of GABA-A receptors. Ganaxolone (3α-hydroxy-3β-methyl-5α-pregnan-20-one, GX) and synthetic analogs of the neurosteroid allopregnanolone (AP) are designed to treat epilepsy and related conditions. However, their precise mechanism of action in native neurons remains unclear. Here, we sought to determine the mode of action of GX and its analogs at GABA-A receptors in native hippocampal neurons by analyzing extrasynaptic receptor-mediated tonic currents and synaptic receptor-mediated phasic currents...
March 30, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29593561/reciprocal-interactions-of-mitochondria-and-the-neuroimmunoendocrine-system-in-neurodegenerative-disorders-an-important-role-for-melatonin-regulation
#19
REVIEW
Victoria O Polyakova, Igor M Kvetnoy, George Anderson, Jessica Rosati, Gianluigi Mazzoccoli, Natalya S Linkova
Structural and functional alterations of mitochondria are intimately linked to a wide array of medical conditions. Many factors are involved in the regulation of mitochondrial function, including cytokines, chaperones, chemokines, neurosteroids, and ubiquitins. The role of diffusely located cells of the neuroendocrine system, including biogenic amines and peptide hormones, in the management of mitochondrial function, as well as the role of altered mitochondrial function in the regulation of these cells and system, is an area of intense investigation...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29577884/regional-specific-effects-of-cerebral-ischemia-reperfusion-and-dehydroepiandrosterone-on-synaptic-nmdar-psd-95-complex-in-male-wistar-rats
#20
Marina Zaric, Dunja Drakulic, Ivana Gusevac Stojanovic, Natasa Mitrovic, Ivana Grkovic, Jelena Martinovic
Excessive glutamate efflux and N-methyl-D-aspartate receptor (NMDAR) over-activation represent well-known hallmarks of cerebral ischemia/reperfusion (I/R) injury, still, expression of proteins involved in this aspect of I/R pathophysiology show inconsistent data. Neurosteroid dehydroepiandrosterone (DHEA) has been proposed as potent NMDAR modulator, but its influence on I/R-induced changes up to date remains questionable. Therefore, I/R-governed alteration of vesicular glutamate transporter 1 (vGluT1), synaptic NMDAR subunit composition, postsynaptic density protein 95 (PSD-95) and neuronal morphology alone or following DHEA treatment were examined...
March 22, 2018: Brain Research
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