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https://www.readbyqxmd.com/read/28720517/transient-receptor-potential-trpm3-channels-pharmacology-signaling-and-biological-functions
#1
REVIEW
Gerald Thiel, Sandra Rubil, Andrea Lesch, Lisbeth A Guethlein, Oliver G Rössler
The transient receptor potential melastatin-3 (TRPM3) channel belongs to the family of transient receptor potential (TRP) cation channels that are expressed in a variety of tissues and cell types, including dorsal root ganglia, cardiomyocytes and pancreatic beta-cells. Although its natural ligands are currently unknown, TRPM3 channels can be activated by the neurosteroid pregnenolone sulfate, the synthetic ligand CIM0216, and by noxious heat. TRPM3 channels are regulated by phosphoinositides, and perhaps by calmodulin...
July 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28707553/ziram-inhibits-rat-neurosteroidogenic-5%C3%AE-reductase-1-and-3%C3%AE-hydroxysteroid-dehydrogenase
#2
Ying Su, Huitao Li, Xiaomin Chen, Yiyan Wang, Xiaoheng Li, Jianliang Sun, Ren-Shan Ge
The neurotoxicity of ziram is largely unknown. In this study, we investigated the direct inhibitions of ziram on rat neurosteroid synthetic and metabolizing enzymes, 5α-reductase 1 (SRD5A1), 3α-hydroxysteroid dehydrogenase (AKR1C14), and retinol dehydrogenase 2 (RDH2). Rat SRD5A1, AKR1C14, and RDH2 were cloned and transiently expressed in COS1 cells, and the effects of ziram on these enzymes were measured. Ziram inhibited rat SRD5A1 and AKR1C14 with IC50 values of 1.556 ± 0.078 and 1.017 ± 0.072 μM, respectively, when 1000 nM steroid substrates were used...
July 14, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28707358/suppressed-oligodendrocyte-steroidogenesis-in-multiple-sclerosis-implications-for-regulation-of-neuroinflammation
#3
Roobina Boghozian, Brienne A McKenzie, Leina B Saito, Ninad Mehta, William G Branton, JianQiang Lu, Glen B Baker, Farshid Noorbakhsh, Christopher Power
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Neurosteroids are reported to exert anti-inflammatory effects in several neurological disorders. We investigated the expression and actions of the neurosteroid, dehydroepiandrosterone (DHEA), and its more stable 3β-sulphated ester, DHEA-S, in MS and associated experimental models. CNS tissues from patients with MS and animals with experimental autoimmune encephalomyelitis (EAE) displayed reduced DHEA concentrations, accompanied by diminished expression of the DHEA-synthesizing enzyme CYP17A1 in oligodendrocytes (ODCs), in association with increased expression of inflammatory genes including interferon (IFN)-γ and interleukin (IL)-1β...
July 14, 2017: Glia
https://www.readbyqxmd.com/read/28707277/open-label-allopregnanolone-treatment-of-men-with-fragile-x-associated-tremor-ataxia-syndrome
#4
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/28704441/a-comparison-of-sex-steroid-concentration-levels-in-the-vitreous-and-serum-of-patients-with-vitreoretinal-diseases
#5
Yuko Nishikawa, Seita Morishita, Taeko Horie, Masanori Fukumoto, Takaki Sato, Teruyo Kida, Hidehiro Oku, Jun Sugasawa, Tsunehiko Ikeda, Kimitoshi Nakamura
The purpose of this study was to compare steroid hormone concentration levels in the vitreous and serum of vitreoretinal disease patients to elucidate the possibility of neurosteroid production in the retina. Serum and vitreous samples were collected from vitrectomy patients, and estradiol (E2) and testosterone (T) concentrations were measured using electro-chemiluminescence immunoassay. We measured E2 in epiretinal membrane (ERM, n = 14), macular hole (MH, n = 18), proliferative diabetic retinopathy (PDR, n = 20), and retinal detachment (RD, n = 19) cases, and T in ERM (n = 14), MH (n = 17), PDR (n = 13), and RD (n = 17) cases...
2017: PloS One
https://www.readbyqxmd.com/read/28686904/gender-differences-in-susceptibility-to-schizophrenia-potential-implication-of-neurosteroids
#6
Yu-Chi Huang, Chi-Fa Hung, Pao-Yen Lin, Yu Lee, Chih-Ching Wu, Su-Ting Hsu, Chien-Chih Chen, Mian-Yoon Chong, Chieh-Hsin Lin, Liang-Jen Wang
Past research has indicated gender differences in the clinical characteristics and course of schizophrenia. In this study, we investigated whether gender differences in the manifestation of schizophrenia are correlated with neurosteroids, including dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and pregnenolone. We further explored the potential relationship between the aforementioned neurosteroids and psychopathology. We recruited 65 schizophrenic patients (36 males and 29 females) and 103 healthy control subjects (47 males and 56 females) and obtained blood samples from the subjects in the morning while in a fasting state to determine the serum levels of DHEA, DHEA-S, and pregnenolone...
June 26, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28675779/neurosteroidogenesis-and-progesterone-anti-inflammatory-neuroprotective-effects
#7
REVIEW
Alejandro F De Nicola, Laura I Garay, Maria Meyer, Rachida Guennoun, Regine Sitruk-Ware, Michael Schumacher, Maria Claudia Gonzalez Deniselle
Progesterone shows anti-inflammatory and promyelinating effects in mice with autoimmune experimental encephalomyelitis (EAE), a commonly used model for multiple sclerosis (MS). Since neurosteroids have been implicated as protective factors for MS and EAE, we analyzed the expression of neurosteroidogenic enzymes in the compromised spinal cord of EAE mice. EAE was induced in female C57Bl6 mice and killed on day 16 after induction. Progesterone was given by pellet implantation 1 week before EAE induction. Untreated EAE mice showed decreased mRNAs for the steroidogenic acute regulatory protein (Star), voltage-dependent anion channel (VDAC), cholesterol side-chain cleavage (P450scc), 5α-reductase, 3α-hydroxysteroid dehydrogenase (3α-HSOR) and aromatase, whereas changes of 3β-hydroxysteroid dehydrogenase (3β-HSD) were not significant...
July 4, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28666923/allopregnanolone-levels-and-depressive-symptoms-during-pregnancy-in-relation-to-single-nucleotide-polymorphisms-in-the-allopregnanolone-synthesis-pathway
#8
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)...
June 27, 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
#9
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/28660203/the-neuroprotective-steroid-progesterone-promotes-mitochondrial-uncoupling-reduces-cytosolic-calcium-and-augments-stress-resistance-in-yeast-cells
#10
Slaven Stekovic, Christoph Ruckenstuhl, Philipp Royer, Christof Winkler-Hermaden, Didac Carmona-Gutierrez, Kai-Uwe Fröhlich, Guido Kroemer, Frank Madeo
The steroid hormone progesterone is not only a crucial sex hormone, but also serves as a neurosteroid, thus playing an important role in brain function. Epidemiological data suggest that progesterone improves the recovery of patients after traumatic brain injury. Brain injuries are often connected to elevated calcium spikes, reactive oxygen species (ROS) and programmed cell death affecting neurons. Here, we establish a yeast model to study progesterone-mediated cytoprotection. External supply of progesterone protected yeast cells from apoptosis-inducing stress stimuli and resulted in elevated mitochondrial oxygen uptake accompanied by a drop in ROS generation and ATP levels during chronological aging...
May 31, 2017: Microbial Cell
https://www.readbyqxmd.com/read/28655644/pregnenolone-does-not-interfere-with-the-effects-of-cannabinoids-on-synaptic-transmission-in-the-cerebellum-and-the-nucleus-accumbens
#11
Anna Krohmer, Martin Brehm, Volker Auwärter, Bela Szabo
The steroid hormone pregnenolone attenuates several in vivo behavioural and somatic effects of the phytocannabinoid Δ(9)-tetrahydrocannabinol, and it was suggested that pregnenolone can protect the brain from cannabis intoxication. The primary neuronal cannabinoid action behind most of the behavioural and somatic effects of cannabinoids is presynaptic inhibition of synaptic transmission. Therefore, the hypothesis of the present study was that pregnenolone attenuates the inhibition of synaptic transmission elicited by cannabinoids...
June 24, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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
#12
Lei Li, Wei Wang, Li-Ming Zhang, Xiang-Yun Jiang, Shuzheng Sun, Li-Jun Sun, Ying Guo, Jie Gong, Youzhi Zhang, Henglin Wang, Yunfeng 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/28652501/serum-levels-of-neuroactive-steroids-in-first-episode-antipsychotic-na%C3%A3-ve-schizophrenic-patients-and-its-correlation-with-aggression-a-case-control-study
#13
R K Solanki, P Sharma, A Tyagi, C Singh
BACKGROUND: The evidence of hypothalamic-pituitary-adrenal axis dysfunction in schizophrenia has been reviewed in the context of the stress-diathesis model. Overactivation of this axis leads to altered blood levels of cortisol and dehydroepiandrosterone sulfate (DHEA-S). These neurosteroids in turn act on the hippocampus and interact with gamma-aminobutyric acid and N-methyl-D-aspartate receptors leading to neurotoxicity and may be involved in the neurobiology of aggression. This study aimed to explore the blood level of these neurosteroids and ascertain its correlation with state aggression and psychopathology in first-episode antipsychotic-naïve schizophrenic patients...
June 2017: East Asian Archives of Psychiatry: Official Journal of the Hong Kong College of Psychiatrists
https://www.readbyqxmd.com/read/28641386/the-neurosteroid-pregnenolone-reverts-microtubule-derangement-induced-by-the-loss-of-a-functional-cdkl5-iqgap1-complex
#14
Isabella Barbiero, Diana Peroni, Marco Tramarin, Chetan Chandola, Laura Rusconi, Nicoletta Landsberger, Charlotte Kilstrup-Nielsen
CDKL5 is a protein kinase that plays a key role for neuronal functions as testified by the onset of complex neuronal dysfunctions in patients with genetic lesions in CDKL5. Here we identify a novel interactor of CDKL5, IQGAP1, a fundamental regulator of cell migration and polarity. In accordance with a functional role of this interaction, depletion of CDKL5 impairs cell migration and impedes the localization of IQGAP1 at the leading edge. Moreover, we demonstrate that CDKL5 is required for IQGAP1 to form a functional complex with its effectors, Rac1 and the microtubule plus end tracking protein CLIP170...
June 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28617705/liver-x-receptor-%C3%AE-is-involved-in-counteracting-mechanical-allodynia-by-inhibiting-neuroinflammation-in-the-spinal-dorsal-horn
#15
Jing Xu, Yi-Wei Feng, Ling Liu, Wei Wang, Xiong-Xiong Zhong, Xu-Hong Wei, Xian-Guo Liu
BACKGROUND: Liver X receptors, including α and β isoforms, are ligand-activated transcription factors. Whether liver X receptor α plays a role in neuropathic pain is unknown. METHODS: A spared nerve injury model was established in adult male rats and mice. Von Frey tests were performed to evaluate the neuropathic pain behavior; Western blot and immunohistochemistry were performed to understand the underlying mechanisms. RESULTS: Intrathecal injection of a specific liver X receptor agonist T0901317 or GW3965 could either prevent the development of mechanical allodynia or alleviate the established mechanical allodynia, both in rats and wild-type mice...
June 15, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28611376/allopregnanolone-mediates-the-exacerbation-of-tourette-like-responses-by-acute-stress-in-mouse-models
#16
Laura J Mosher, Sean C Godar, Marianela Nelson, Stephen C Fowler, Graziano Pinna, Marco Bortolato
Tourette syndrome (TS) is a neuropsychiatric disorder characterized by multiple tics and sensorimotor abnormalities, the severity of which is typically increased by stress. The neurobiological underpinnings of this exacerbation, however, remain elusive. We recently reported that spatial confinement (SC), a moderate environmental stressor, increases tic-like responses and elicits TS-like sensorimotor gating deficits in the D1CT-7 mouse, one of the best-validated models of TS. Here, we hypothesized that these adverse effects may be mediated by neurosteroids, given their well-documented role in stress-response orchestration...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28599922/vitamin-d-improves-functional-outcomes-in-neonatal-hypoxic-ischemic-male-rats-treated-with-n-acetylcysteine-and-hypothermia
#17
Danielle W Lowe, Jamie L Fraser, Laura Grace Rollins, Jessica Bentzley, Xingju Nie, Renee Martin, Inderjit Singh, Dorothea Jenkins
Hypothermia treatment neuroprotects approximately 50% of neonates who present with moderate to severe hypoxic ischemic encephalopathy (HIE). N-acetylcysteine (NAC), a potent antioxidant, is neuroprotective in combination with hypothermia in neonatal hypoxia-ischemia (HI) female rats, but less protective in males. Vitamin D is a neurosteroid, which may provide immunomodulation and improve outcomes for both sexes. We investigated the efficacy of this combination of drugs with hypothermia after severe HI, as well as potential mechanisms of vitamin D effects in the transition to chronic inflammation...
June 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28589168/first-in-man-allopregnanolone-use-in-super-refractory-status-epilepticus
#18
Henrikas Vaitkevicius, Aatif M Husain, Eric S Rosenthal, Jonathan Rosand, Wendell Bobb, Kiran Reddy, Michael A Rogawski, Andrew J Cole
Super-refractory status epilepticus (SRSE) is associated with high morbidity and mortality. Treatment of SRSE is complicated by progressive cortical hyperexcitability believed to result in part from synaptic GABA receptor internalization and desensitization. Allopregnanolone, a neurosteroid that positively modulates synaptic and extrasynaptic GABAA receptors, has been proposed as a novel treatment. We describe the first two patients with SRSE who were each successfully treated with a 120-h continuous infusion of allopregnanolone...
June 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28581152/neurosteroid-dehydroepiandrosterone-enhances-activity-and-trafficking-of-astrocytic-glt-1-via-%C3%AF-1-receptor-mediated-pkc-activation-in-the-hippocampal-dentate-gyrus-of-rats
#19
Tingting Chen, Motoki Tanaka, Ya Wang, Sha Sha, Kishio Furuya, Ling Chen, Masahiro Sokabe
Neurosteroid dehydroepiandrosterone (DHEA) has been reported to exert a potent neuroprotective effect against glutamate-induced excitotoxicity. However, the underlying mechanism remains to be elucidated. One of the possible mechanisms may be an involvement of astrocytic glutamate transporter subtype-1 (GLT-1) that can quickly clear spilled glutamate at the synapse to prevent excitotoxicity. To examine the effect of DHEA on GLT-1 activity, we measured synaptically induced glial depolarization (SIGD) in the dentate gyrus (DG) of adult rats by applying an optical recording technique to the hippocampal slices stained with voltage-sensitive dye RH155...
September 2017: Glia
https://www.readbyqxmd.com/read/28579120/vitamin-d-and-the-brain-genomic-and-non-genomic-actions
#20
REVIEW
Xiaoying Cui, Helen Gooch, Alice Petty, John J McGrath, Darryl Eyles
1,25(OH)2D3 (vitamin D) is well-recognized as a neurosteroid that modulates multiple brain functions. A growing body of evidence indicates that vitamin D plays a pivotal role in brain development, neurotransmission, neuroprotection and immunomodulation. However, the precise molecular mechanisms by which vitamin D exerts these functions in the brain are still unclear. Vitamin D signalling occurs via the vitamin D receptor (VDR), a zinc-finger protein in the nuclear receptor superfamily. Like other nuclear steroids, vitamin D has both genomic and non-genomic actions...
June 1, 2017: Molecular and Cellular Endocrinology
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