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https://www.readbyqxmd.com/read/28319848/treatment-of-premenstrual-dysphoric-disorder-with-the-gabaa-receptor-modulating-steroid-antagonist-sepranolone-uc1010-a-randomized-controlled-trial
#1
Marie Bixo, Karin Ekberg, Inger Sundström Poromaa, Angelica Lindén Hirschberg, Aino Fianu Jonasson, Lotta Andréen, Erika Timby, Marianne Wulff, Agneta Ehrenborg, Torbjörn Bäckström
CONTEXT: Allopregnanolone is a metabolite from progesterone and a positive modulator of the GABAA receptor. This endogenous steroid may induce negative mood in sensitive women when present in serum levels comparable to the premenstrual phase. Its endogenous isomer, isoallopregnanolone, has been shown to antagonize allopregnanolone effects in experimental animal and human models. OBJECTIVE: The objective was to test whether inhibition of allopregnanolone by treatment with the GABAA modulating steroid antagonist (GAMSA) Sepranolone (UC1010) during the premenstrual phase could reduce symptoms of the premenstrual dysphoric disorder (PMDD)...
March 1, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28316115/gabaa-and-gabab-receptor-dysregulation-in-superior-frontal-cortex-of-subjects-with-schizophrenia-and-bipolar-disorder
#2
S Hossein Fatemi, Timothy D Folsom, Paul D Thuras
Schizophrenia and bipolar disorder are complex psychiatric disorders that affect millions of people worldwide. Evidence from gene association and postmortem studies has identified abnormalities of the gamma-aminobutyric acid (GABA) signaling system in both disorders. Abnormal GABAergic signaling and transmission could contribute to the symptomatology of these disorders, potentially through impaired gamma oscillations which normally occur during cognitive processing. In the current study, we examined the protein expression of 14 GABAA and two GABAB receptor subunits in the superior frontal cortex of subjects with schizophrenia, bipolar disorder, and healthy controls...
March 18, 2017: Synapse
https://www.readbyqxmd.com/read/28301408/k-cl-cotransporter-2-mediated-cl-extrusion-determines-developmental-stage-dependent-impact-of-propofol-anesthesia-on-dendritic-spines
#3
Martin Puskarjov, Hubert Fiumelli, Adrian Briner, Timea Bodogan, Kornel Demeter, Claudia-Marvine Lacoh, Martina Mavrovic, Peter Blaesse, Kai Kaila, Laszlo Vutskits
BACKGROUND: General anesthetics potentiating γ-aminobutyric acid (GABA)-mediated signaling are known to induce a persistent decrement in excitatory synapse number in the cerebral cortex when applied during early postnatal development, while an opposite action is produced at later stages. Here, the authors test the hypothesis that the effect of general anesthetics on synaptogenesis depends upon the efficacy of GABA receptor type A (GABAA)-mediated inhibition controlled by the developmental up-regulation of the potassium-chloride (K-Cl) cotransporter 2 (KCC2)...
March 16, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28299900/development-of-a-robust-mammalian-cell-based-assay-for-studying-recombinant-%C3%AE-4-%C3%AE-1-3-%C3%AE-gabaa-receptor-subtypes
#4
Christina B Falk-Petersen, Rikke Søgaard, Kenneth L Madsen, Anders B Klein, Bente Frølund, Petrine Wellendorph
δ-Containing GABAA receptors are located extrasynaptically and mediate tonic inhibition. Their involvement in brain physiology positions them as interesting drug targets. There is thus a continued interest in establishing reliable recombinant expression systems for δ-containing GABAA receptors. Inconveniently, the recombinant expression of especially α4 β1/3 δ receptors has been found to be notoriously difficult, due to mixed receptor populations and/or stoichiometries and differential pharmacology depending on the expression system used...
March 16, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28299422/homeostatic-regulation-through-gaba-and-acetylcholine-muscarinic-receptors-of-motor-trigeminal-neurons-following-sleep-deprivation
#5
Hanieh Toossi, Esther Del Cid-Pellitero, Barbara E Jones
Muscle tone is regulated across sleep-wake states, being maximal in waking, reduced in slow wave sleep (SWS) and absent in paradoxical or REM sleep (PS or REMS). Such changes in tone have been recorded in the masseter muscles and shown to correspond to changes in activity and polarization of the trigeminal motor 5 (Mo5) neurons. The muscle hypotonia and atonia during sleep depend in part on GABA acting upon both GABAA and GABAB receptors (Rs) and acetylcholine (ACh) acting upon muscarinic 2 (AChM2) Rs. Here, we examined whether Mo5 neurons undergo homeostatic regulation through changes in these inhibitory receptors following prolonged activity with enforced waking...
March 15, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28293190/gaba-selank-and-olanzapine-affect-the-expression-of-genes-involved-in-gabaergic-neurotransmission-in-imr-32-cells
#6
Elena Filatova, Anastasiya Kasian, Timur Kolomin, Ekaterina Rybalkina, Anelya Alieva, Lyudmila Andreeva, Svetlana Limborska, Nikolay Myasoedov, Galina Pavlova, Petr Slominsky, Maria Shadrina
Clinical studies have shown that Selank had an anxiolytic effect comparable to that of classical benzodiazepine drugs, which can enhance the inhibitory effect of GABA by allosteric modulation of GABAA receptors. These data suggest that the molecular mechanism of the effect of Selank may also be related to its ability to affect the performance of the GABAergic system. To test this hypothesis, we studied the changes in expression of 84 genes involved in the functioning of the GABAergic system and in the processes of neurotransmission in the culture of neuroblastoma IMR-32 cells using qPCR method...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28292881/evidence-for-a-histaminergic-input-from-the-ventral-tuberomammillary-nucleus-to-the-solitary-tract-nucleus-involved-in-arterial-pressure-regulation
#7
Ko Yamanaka, Sabine S Gouraud, Miwa Takagishi, Akira Kohsaka, Masanobu Maeda, Hidefumi Waki
The tuberomammillary nucleus (TMN) of the posterior hypothalamus has a high density of histaminergic neurons, the projection fibers of which are present in many areas of the brain, including the nucleus tractus solitarius (NTS), which controls arterial pressure (AP). In this study, we investigated whether the TMN-NTS pathway is involved in central cardiovascular regulation. Bicuculline, a gamma-aminobutyric acid type A (GABAA) receptor antagonist, was microinjected into the ventral TMN of anesthetized rats and its effects on AP and heart rate (HR) were observed...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28292717/test-retest-reproducibility-of-quantitative-binding-measures-of-11-c-ro15-4513-a-pet-ligand-for-gabaa-receptors-containing-alpha5-subunits
#8
Colm J McGinnity, Daniela A Riaño Barros, Lula Rosso, Mattia Veronese, Gaia Rizzo, Alessandra Bertoldo, Rainer Hinz, Federico E Turkheimer, Matthias J Koepp, Alexander Hammers
INTRODUCTION: Alteration of γ-aminobutyric acid "A" (GABAA) receptor-mediated neurotransmission has been associated with various neurological and psychiatric disorders. [(11)C]Ro15-4513 is a PET ligand with high affinity for α5-subunit-containing GABAA receptors, which are highly expressed in limbic regions of the human brain (Sur et al., 1998). We quantified the test-retest reproducibility of measures of [(11)C]Ro15-4513 binding derived from six different quantification methods (12 variants)...
March 11, 2017: NeuroImage
https://www.readbyqxmd.com/read/28288901/trigeminal-brainstem-modulation-of-persistent-orbicularis-oculi-muscle-activity-in-a-rat-model-of-dry-eye
#9
Mostafeezur Rahman, Kazunari Shiozaki, Keiichiro Okamoto, Randall Thompson, David A Bereiter
Altered corneal reflex activity is a common feature of dry eye disease (DE). Trigeminal sensory nerves supply the ocular surface and terminate at the trigeminal interpolaris/caudalis (ViVc) transition and spinomedullary (VcC1) regions. Although both regions contribute to corneal reflexes, their role under dry eye conditions is not well defined. This study assessed the influence of local inhibitory and excitatory amino acid neurotransmission at the ViVc transition and VcC1 regions on hypertonic saline (HS) evoked orbicularis oculi muscle activity (OOemg) in urethane-anesthetized male rats after exorbital gland removal (DE)...
March 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28288863/toluene-s-effects-on-activity-and-extracellular-dopamine-in-the-mouse-are-altered-by-gabaa-antagonism
#10
Sean P Callan, Aaron K Apawu, Tiffany A Mathews, Scott E Bowen
The abuse of inhalants like toluene continues to be widespread around the world, especially among children and teenagers. Despite its frequency of misuse, the dynamics between dopamine (DA) and gamma-aminobutyric acid (GABA) in response to toluene exposure remains unclear. To further decipher toluene's actions, we used a dynamic exposure system in combination with microdialysis to examine in vivo the effects of acutely inhaled toluene on DA release within the mouse caudate putamen (CPu). Results show that toluene inhalation produced increases in DA levels and locomotor activity...
March 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28288780/neuroprotective-effects-of-gabaergic-phenols-correlated-with-their-pharmacological-and-antioxidant-properties
#11
Leticia Delgado-Marín, Mariela Sánchez-Borzone, Daniel A García
AIMS: Various investigations have demonstrated the protective capacity of general anesthetics as neuroprotective agents. The effects of propofol against ischemia are known to reside in its antioxidant properties and its GABAergic activity. Other aromatic alcohols have also been reported as able to protect neurons against oxidative damage. The aim of this work is to evaluate the potential neuroprotective effect of some phenols, structurally analogues of propofol, with proven GABAergic activity...
March 10, 2017: Life Sciences
https://www.readbyqxmd.com/read/28286184/altered-functional-efficacy-of-hippocampal-interneuron-during-epileptogenesis-following-febrile-seizures
#12
Yeon Hee Yu, Kahyun Lee, Dal Sik Sin, Kyung-Ho Park, Dae-Kyoon Park, Duk-Soo Kim
Febrile seizure (FS) is the most common seizure type in infants and young children. FS may induce functional changes in the hippocampal circuitries. Abnormality of excitatory and inhibitory neurotransmissions was previously related to wide-spread seizure attack in the hippocampus following recurrent seizure onset. To clarify the involvement of expressional changes and functional alterations of hippocampal interneurons with epileptogenesis following FS, we investigated long-term effects following recurrent seizure in a hyperthermia-induced seizure animal model...
March 7, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28285889/influence-of-inter-train-interval-on-the-plastic-effects-of-rtms
#13
Robin F H Cash, Aisha Dar, Jeanette Hui, Leo De Ruiter, Julianne Baarbé, Peter Fettes, Sarah Peters, Paul B Fitzgerald, Jonathan Downar, Robert Chen
BACKGROUND: High frequency repetitive transcranial magnetic stimulation (rTMS) elicits plastic effects in excitatory and inhibitory circuits. Inter-train intervals (ITI) were initially incorporated into rTMS paradigms to avoid overheating and for safety considerations. Recent studies have shown that inclusion of ITI, as opposed to continuous stimulation, is essential for eliciting excitatory effects, but the optimal ITI remains unknown. Moreover, if ITI duration has no effect, it may be possible to substantially reduce treatment time for rTMS...
March 2, 2017: Brain Stimulation
https://www.readbyqxmd.com/read/28285877/neurotransmitter-regulated-regeneration-in-the-zebrafish-retina
#14
Mahesh B Rao, Dominic Didiano, James G Patton
Current efforts to repair damaged or diseased mammalian retinas are inefficient and largely incapable of fully restoring vision. Conversely, the zebrafish retina is capable of spontaneous regeneration upon damage using Müller glia (MG)-derived progenitors. Understanding how zebrafish MG initiate regeneration may help develop new treatments that prompt mammalian retinas to regenerate. We show that inhibition of γ-aminobutyric acid (GABA) signaling facilitates initiation of MG proliferation. GABA levels decrease following damage, and MG are positioned to detect decreased ambient levels and undergo dedifferentiation...
March 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28284708/visual-experience-regulates-the-development-of-long-term-synaptic-modifications-induced-by-low-frequency-stimulation-in-mouse-visual-cortex
#15
Taketoshi Sugimura, Mariko Yamamoto, Kazumasa Yamada, Yukio Komatsu, Yumiko Yoshimura
Manipulation of visual experience can considerably modify visual responses of visual cortical neurons even in adulthood in the mouse, although the modification is less profound than that observed during the critical period. Our previous studies demonstrated that low-frequency (2Hz) stimulation for 15minutes applied to layer 4 induces T-type Ca(2+) channel-dependent long-term potentiation (LTP) at excitatory synapses in layer 2/3 neurons of visual cortex during the critical period. In this study, we investigated whether low-frequency stimulation could induce synaptic plasticity in adult mice...
March 8, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28279354/garlh-family-proteins-stabilize-gabaa-receptors-at-synapses
#16
Tokiwa Yamasaki, Erika Hoyos-Ramirez, James S Martenson, Megumi Morimoto-Tomita, Susumu Tomita
Ionotropic neurotransmitter receptors mediate fast synaptic transmission by functioning as ligand-gated ion channels. Fast inhibitory transmission in the brain is mediated mostly by ionotropic GABAA receptors (GABAARs), but their essential components for synaptic localization remain unknown. Here, we identify putative auxiliary subunits of GABAARs, which we term GARLHs, consisting of LH4 and LH3 proteins. LH4 forms a stable tripartite complex with GABAARs and neuroligin-2 in the brain. Moreover, LH4 is required for the synaptic localization of GABAARs and inhibitory synaptic transmission in the hippocampus...
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28279020/kcc2-downregulation-facilitates-epileptic-seizures
#17
Lulan Chen, Li Wan, Zheng Wu, Wanting Ren, Yian Huang, Binbin Qian, Yun Wang
GABAA receptor-mediated inhibition depends on the maintenance of low level intracellular [Cl(-)] concentration, which in adult depends on neuron specific K(+)-Cl(-) cotransporter-2 (KCC2). Previous studies have shown that KCC2 was downregulated in both epileptic patients and various epileptic animal models. However, the temporal relationship between KCC2 downregulation and seizure induction is unclear yet. In this study, we explored the temporal relationship and the influence of KCC2 downregulation on seizure induction...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28275709/caudal-nucleus-accumbens-core-is-critical-in-the-regulation-of-cue-elicited-approach-avoidance-decisions
#18
Laurie Hamel, Tharshika Thangarasa, Osai Samadi, Rutsuko Ito
The nucleus accumbens (NAc) is thought to be a site of integration of positively and negatively valenced information and action selection. Functional differentiation in valence processing has previously been found along the rostrocaudal axis of the shell region of the NAc in assessments of unconditioned motivation. Given that the core region of the NAc has been implicated in the elicitation of motivated behavior in response to conditioned cues, we sought to assess the role of caudal, intermediate, and rostral sites within this subregion in cue-elicited approach-avoidance decisions...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28274653/effects-of-chemical-stimulation-of-the-lateral-wings-of-the-dorsal-raphe-nucleus-on-panic-like-defensive-behaviors-and-fos-protein-expression-in-rats
#19
Melina Matthiesen, Ailton Spiacci, Hélio Zangrossi
The lateral wings subnucleus of the dorsal raphe nucleus (lwDR) has been implicated in the modulation of panic-like behaviors, such as escape. Infusion of non- excitotoxic doses of the excitatory amino acid kainic acid into this subnucleus promptly evokes a vigorous escape response. In addition, rats exposed to panic-inducing situations show an increase in Fos protein expression in neurons within the lwDR. In the present study, we first investigated whether key structures associated with the mediation of escape behavior are recruited after chemical stimulation of the lwDR with kainic acid...
March 6, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28273868/pharmacological-potential-and-synthetic-approaches-of-imidazo-4-5-b-pyridine-and-imidazo-4-5-c-pyridine-derivatives
#20
REVIEW
Malwina Krause, Henryk Foks, Katarzyna Gobis
The structural resemblance between the fused imidazopyridine heterocyclic ring system and purines has prompted biological investigations to assess their potential therapeutic significance. They are known to play a crucial role in numerous disease conditions. The discovery of their first bioactivity as GABAA receptor positive allosteric modulators divulged their medicinal potential. Proton pump inhibitors, aromatase inhibitors, and NSAIDs were also found in this chemical group. Imidazopyridines have the ability to influence many cellular pathways necessary for the proper functioning of cancerous cells, pathogens, components of the immune system, enzymes involved in carbohydrate metabolism, etc...
March 4, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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