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https://www.readbyqxmd.com/read/28416442/allopregnanolone-decreases-interictal-spiking-and-fast-ripples-in-an-animal-model-of-mesial-temporal-lobe-epilepsy
#1
Maxime Lévesque, Rochelle Herrington, Leila Leclerc, Michael A Rogawski, Massimo Avoli
The objective of this study was to characterize the impact of allopregnanolone, a neurosteroid that acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors, on interictal spikes and high-frequency oscillations (ripples: 80-200 Hz, fast ripples: 250-500 Hz) in the pilocarpine model of mesial temporal lobe epilepsy. Seven out of 25 Sprague-Dawley rats experiencing 1 h of pilocarpine-induced status epilepticus (SE) began treatment with allopregnanolone (9.6-12.8 mg/kg/day) on the following day...
April 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28414121/neural-derived-estradiol-regulates-brain-plasticity
#2
REVIEW
Iñigo Azcoitia, Maria Angeles Arevalo, Luis M Garcia-Segura
In addition to be an ovarian hormone, estradiol is a neurosteroid synthesized by neural cells. The brain is a steroidogenic tissue that metabolizes testosterone to estradiol. The last step in the synthesis of estradiol is catalyzed by the enzyme aromatase, which is widely expressed in the brain of male and female animals and humans. Studies that have manipulated the expression or the activity of aromatase have revealed that brain-derived estradiol acts as a neuromodulator and regulates different forms of brain plasticity in male and female animals...
April 13, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28412873/%C3%AE-3-adrenergic-receptors-adipokines-and-neuroendocrine-activation-during-stress-induced-by-repeated-immune-challenge-in-male-and-female-rats
#3
Agnesa Csanova, Natasa Hlavacova, Malgorzata Hasiec, Michal Pokusa, Barbora Prokopova, Daniela Jezova
The main hypothesis of the study is that stress associated with repeated immune challenge has an impact on β3-adrenergic receptor gene expression in the brain. Sprague-Dawley rats were intraperitoneally injected with increasing doses of lipopolysaccharide (LPS) for 5 consecutive days. LPS treatment was associated with body weight loss and increased anxiety-like behavior. In LPS-treated animals of both sexes, β3-receptor gene expression was increased in the prefrontal cortex but not the hippocampus. LPS treatment decreased β3-receptor gene expression in white adipose tissue with higher values in males compared to females...
April 16, 2017: Stress: the International Journal on the Biology of Stress
https://www.readbyqxmd.com/read/28407365/role-of-allopregnanolone-biosynthesis-in-acute-stress-induced-anxiety-like-behaviors-in-mice
#4
Kazumi Yoshizawa, Ayano Okumura, Kozue Nakashima, Tomoyo Sato, Tatsuya Higashi
The neurosteroid allopregnanolone (3α, 5α-tetra-hydroprogesterone: ALLO) elicits anxiolytic, anticonvulsant, and hypnotic anesthetic effects in vivo similar to those induced by other positive allosteric modulators of the GABAA receptor. Endogenous ALLO has been shown to be rapidly elevated in the brain by acute stress paradigms, such as immobilization, in animal models. The present study was designed to ascertain the role of neurosteroid biosynthesis in the anxiety-like behavior induced by immobilization stress...
April 13, 2017: Synapse
https://www.readbyqxmd.com/read/28374007/contribution-of-resting-conductance-gabaa-receptor-mediated-miniature-synaptic-currents-and-neurosteroid-to-chloride-homeostasis-in-central-neurons
#5
Tushar D Yelhekar, Michael Druzin, Staffan Johansson
Maintenance of a low intraneuronal Cl(-) concentration, [Cl(-)]i, is critical for inhibition in the CNS. Here, the contribution of passive, conductive Cl(-) flux to recovery of [Cl(-)]i after a high load was analyzed in mature central neurons from rat. A novel method for quantifying the resting Cl(-) conductance, important for [Cl(-)]i recovery, was developed and the possible contribution of GABAA and glycine receptors and of ClC-2 channels to this conductance was analyzed. The hypothesis that spontaneous, action potential-independent release of GABA is important for [Cl(-)]i recovery was tested...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28367959/polymorphisms-of-sts-gene-and-sult2a1-gene-and-neurosteroid-levels-in-han-chinese-boys-with-attention-deficit-hyperactivity-disorder-an-exploratory-investigation
#6
Liang-Jen Wang, Wen-Ching Chan, Miao-Chun Chou, Wen-Jiun Chou, Min-Jing Lee, Sheng-Yu Lee, Pao-Yen Lin, Yi-Hsin Yang, Cheng-Fang Yen
This study examined the relationships among polymorphisms of the STS gene and SULT2A1 gene, dehydroepiandrosterone (DHEA) and its sulfated form (DHEA-S), and characteristics of attention-deficit/hyperactivity disorder (ADHD). We used cheek swabs to obtain the genomic DNA of 200 ADHD male probands (mean age: 8.7 years), 192 patients' mothers and 157 patients' fathers. Three SNPs in the STS gene (rs6639786, rs2270112, and rs17268988) and one SNP in the SULT2A1 gene (rs182420) were genotyped. Saliva samples were collected from the ADHD patients to analyze DHEA and DHEA-S levels...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28363987/progesterone-induced-neuroprotection-in-reperfusion-promoted-mitochondrial-dysfunction-following-focal-cerebral-ischemia-in-rats
#7
Syed Suhail Andrabi, Suhel Parvez, Heena Tabassum
Alterations in mitochondrial permeability transition and organelle damage are key players in the development of cerebral ischemic tissue injury due to associated modifications in ATP turnover and cellular apoptosis/necrosis. Early restoration of blood flow and improvement of mitochondrial function might reverse the situation and help in recovery following an onset of stroke. Mitochondria and related bioenergetics can be effectively used as pharmacological targets. Progesterone (P4), one of the promising neurosteroids, has been found neuroprotective in various models of neurological diseases through a number of mechanisms...
March 31, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28356049/calcium-engaged-mechanisms-of-nongenomic-action-of-neurosteroids
#8
Elzbieta Rebas, Tomasz Radzik, Tomasz Boczek, Ludmila Zylinska
Among hundreds of molecules affecting variety of neuronal processes, neurosteroids form the unique group because of their dual mechanism of action. Classically, they bind to intracellular and/or nuclear receptors, and next modify gene transcription. Another mode of action is linked with the rapid effects induced at the plasma membrane level within seconds or milliseconds. The negative and positive modulations have been documented for GABAA receptor complex, glycine receptor, NMDA receptor, AMPA receptor, G protein-coupled receptors and sigma-1 receptor, as well as for several membrane ion channels and plasma membrane enzymes...
March 28, 2017: Current Neuropharmacology
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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