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https://www.readbyqxmd.com/read/28219764/gabaa-receptor-expression-and-white-matter-disruption-in-intrauterine-growth-restricted-piglets
#1
Viskasari P Kalanjati, Julie A Wixey, Stephanie M Miller, Paul B Colditz, Stella T Bjorkman
Intrauterine growth restriction (IUGR) is one of the most common causes of perinatal mortality and morbidity. White matter and neuronal injury are major pathophysiological features of the IUGR neonatal brain. GABAA (γ-aminobutyric acid type A) receptors have been shown to play a role in oligodendrocyte differentiation and proliferation in the neonatal brain and may be a key factor in white matter injury and myelination in IUGR neonates. Whether there are impairments to the GABAergic system and neuronal cytoskeleton in IUGR brain has yet to be elucidated...
February 17, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28218471/%C3%AE-4%C3%AE-%C3%AE-gabaa-receptors-in-dorsal-hippocampal-ca1-of-adolescent-female-rats-traffic-to-the-plasma-membrane-of-dendritic-spines-following-voluntary-exercise-and-contribute-to-protection-of-animals-from-activity-based-anorexia-through-localization-at-excitatory
#2
Chiye Aoki, Yi-Wen Chen, Tara Gunkali Chowdhury, Walter Piper
In hippocampal CA1 of adolescent female rodents, α4βδ-GABAA receptors (α4βδ-GABAA Rs) suppress excitability of pyramidal neurons through shunting inhibition at excitatory synapses. This contributes to anxiolysis of stressed animals. Socially isolated adolescent female rats with 8 days of wheel access, the last 4 days of which entail restricted food access, have been shown to exhibit excessive exercise, choosing to run instead of eat (activity-based anorexia [ABA]). Upregulation of α4βδ-GABAA Rs in the dorsal hippocampal CA1 (DH), seen among some ABA animals, correlates with suppression of excessive exercise...
February 20, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28216893/effects-of-insecticidal-ketones-present-in-mint-plants-on-gabaa-receptor-from-mammalian-neurons
#3
Mariela Eugenia Sánchez-Borzone, Leticia Delgado Marin, Daniel Asmed García
BACKGROUND: The genus Mentha, an important member of the Lamiaceae family, is represented by many species commonly known as mint. The insecticidal activity of Mentha oil and its main components has been tested and established against various insects/pests. Among these, the ketone monoterpenes that are most common in different Mentha species demonstrated insect toxicity, with pulegone being the most active, followed by carvone and menthone. Considering that the GABAA receptor (GABAA-R) is one of the main insecticide targets on neurons, and that pulegone would modulate the insect GABA system, it may be expected that the insecticidal properties of Mentha ketones are mediated by their interaction with this receptor...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28216123/ablation-of-the-auditory-cortex-results-in-changes-in-the-expression-of-neurotransmission-related-mrnas-in-the-cochlea
#4
Verónica Lamas, José M Juiz, Miguel A Merchán
The auditory cortex (AC) dynamically regulates responses of the Organ of Corti to sound through descending connections to both the medial (MOC) and lateral (LOC) olivocochlear efferent systems. We have recently provided evidence that AC has a reinforcement role in the responses to sound of the auditory brainstem nuclei. In a molecular level, we have shown that descending inputs from AC are needed to regulate the expression of molecules involved in outer hair cell (OHC) electromotility control, such as prestin and the α10 nicotinic acetylcholine receptor (nAchR)...
February 16, 2017: Hearing Research
https://www.readbyqxmd.com/read/28215510/short-term-treatment-with-flumazenil-restores-long-term-object-memory-in-a-mouse-model-of-down-syndrome
#5
Damien Colas, Bayarsaikhan Chuluun, Craig C Garner, H Craig Heller
Down syndrome (DS) is a common genetic cause of intellectual disability yet no pro-cognitive drug therapies are approved for human use. Mechanistic studies in a mouse model of DS (Ts65Dn mice) demonstrate that impaired cognitive function is due to excessive neuronal inhibitory tone. These deficits are normalized by chronic, short-term low doses of GABAA receptor (GABAAR) antagonists in adult animals, but none of the compounds investigated are approved for human use. We explored the therapeutic potential of flumazenil (FLUM), a GABAAR antagonist working at the benzodiazepine binding site that has FDA approval...
February 12, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28214522/prelimbic-cortex-extracellular-signal-regulated-kinase-1-2-activation-is-required-for-memory-retrieval-of-long-term-inhibitory-avoidance
#6
Fei Luo, Jian Zheng, Xuan Sun, Wei-Ke Deng, Fang Liu, Bao-Ming Li
Neural mechanism underlying memory retrieval has been extensively studied in the hippocampus and amygdala. However, little is known about the role of medial prefrontal cortex in long-term memory retrieval. We evaluate this issue in one-trial step-through inhibitory avoidance (IA) paradigm. Our results showed that, 1) inactivation of mPFC by local infusion of GABAA-receptor agonist muscimol caused severe deficits in retrieval of 1-day and 7-day but had no effects on 2-hour inhibitory avoidance memory; 2) the protein level of phosphorylated-ERK1/2 in mPFC were significantly increased following retrieval of 1-day and 7-day IA memory, so did the numbers of phosphorylated-ERK (pERK) and phosphorylated-CREB (pCREB) labeled neurons; 3) intra-mPFC infusion of ERK kinase inhibitor PD98095 significantly reduced phosphorylated ERK1/2 levels and phosphorylated-ERK1/2 and phosphorylated-CREB labeled cells, and severely impaired retrieval of 7-day IA memory when the drugs were administrated 30 min prior to test...
February 15, 2017: Brain Research
https://www.readbyqxmd.com/read/28211669/3-aminomethyl-derivatives-of-2-phenylimidazo-1-2-a-pyridine-as-positive-allosteric-modulators-of-gabaa-receptor-with-potential-antipsychotic-activity
#7
Monika Marcinkowska, Marcin Kolaczkowski, Krzysztof Kamiński, Adam Bucki, Maciej Henryk Pawlowski, Agata Siwek, Tadeusz Karcz, Gabriela Starowicz, Karolina Sloczynska, Elżbieta Pękala, Anna Wesołowska, Jerzy Samochowiec, Paweł Mierzejewski, Przemyslaw Bienkowski
Schizophrenia is a mental illness characterized by behavioral changes as well as anatomical and neurochemical abnormalities. There has been a remarkable progress in the drug discovery for schizophrenia; however, antipsychotics that act through molecular targets, other than monoaminergic receptors, have not been developed. One of the hypotheses of schizophrenia states that GABAergic dysfunction might be implemented in the pathophysiology of this disease. Our recent findings and previous clinical observations have suggested that modulation of GABAergic system through α1-GABAA receptors would represent an original approach for the treatment of schizophrenia...
February 17, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28207286/lc-ms-ms-simultaneous-analysis-of-allopregnanolone-epiallopregnanolone-pregnanolone-dehydroepiandrosterone-and-dehydroepiandrosterone-3-sulfate-in-human-plasma
#8
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...
February 16, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28202703/investigations-in-gabaa-receptor-antibody-associated-encephalitis
#9
Marianna Spatola, Mar Petit-Pedrol, Mateus Mistieri Simabukuro, Thaís Armangue, Fernanda J Castro, Maria I Barcelo Artigues, Maria R Julià Benique, Leslie Benson, Mark Gorman, Ana Felipe, Ruben L Caparó Oblitas, Myrna R Rosenfeld, Francesc Graus, Josep Dalmau
OBJECTIVE: To report the clinical features, comorbidities, receptor subunit targets, and outcome in patients with anti-GABAA receptor (GABAAR) encephalitis. METHODS: Clinical study of 26 patients, including 17 new (April 2013-January 2016) and 9 previously reported patients. Antibodies to α1, β3, and γ2 subunits of the GABAAR were determined using reported techniques. RESULTS: Patients' median age was 40.5 years (interquartile range 48...
February 15, 2017: Neurology
https://www.readbyqxmd.com/read/28202580/spinal-disinhibition-in-experimental-and-clinical-painful-diabetic-neuropathy
#10
Andrew G Marshall, Corinne Lee-Kubli, Shazli Azmi, Michael Zhang, Maryam Ferdousi, Teresa Mixcoatl-Zecuatl, Ioannis N Petropoulos, Georgios Ponirakis, Mark S Fineman, Hassan Fadavi, Katie Frizzi, Mitra Tavakoli, Maria Jeziorska, Corinne G Jolivalt, Andrew J M Boulton, Nathan Efron, Nigel A Calcutt, Rayaz A Malik
Impaired rate dependent depression (RDD) of the Hoffman-reflex is associated with reduced dorsal spinal cord potassium chloride co-transporter expression and impaired spinal GABAA receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of impaired RDD in diabetic rodents exhibiting features of painful neuropathy and the translational potential of this marker of spinal inhibitory dysfunction in human painful diabetic neuropathy. Impaired RDD and allodynia were present in type 1 and type 2 diabetic rats but not in rats with type 1 diabetes receiving insulin supplementation that did not restore normoglycemia...
February 15, 2017: Diabetes
https://www.readbyqxmd.com/read/28198153/chronic-stress-in-lizards-studies-on-the-behavior-and-benzodiazepine-receptors-in-liolaemus-koslowskyi-and-cnemidophorus-tergolaevigatus
#11
Alejandra Soloaga, Mariana Pueta, Félix Benjamín Cruz, Jackelyn Melissa Kembro, Raul Hector Marin
Behavioral and physiological adaptive responses of animals facing chronic exposure to a single stressor may allow them to overcome its negative effects for future exposures to similar stressful situations. At chemical level, the GABAA /benzodiazepine complex is considered one of the main receptor systems involved in the modulation of stress-induced responses. Here, we describe the behavioral responses of two different lizard species, Liolaemus koslowskyi and Cnemidophorus tergolaevigatus exposed to three potential chronic stressful treatments: (a) high temperature, (b) forced swimming, and (c) simulated predator...
December 2016: Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology
https://www.readbyqxmd.com/read/28197552/altered-channel-conductance-states-and-gating-of-gabaa-receptors-by-a-pore-mutation-linked-to-dravet-syndrome
#12
Ciria C Hernandez, Weijing Kong, Ningning Hu, Yujia Zhang, Wangzhen Shen, Laurel Jackson, Xiaoyan Liu, Yuwu Jiang, Robert L Macdonald
We identified a de novo missense mutation, P302L, in the γ-aminobutyric acid type A (GABAA) receptor γ2 subunit gene GABRG2 in a patient with Dravet syndrome using targeted next-generation sequencing. The mutation was in the cytoplasmic portion of the transmembrane segment M2 of the γ2 subunit that faces the pore lumen. GABAA receptor α1 and β3 subunits were coexpressed with wild-type (wt) γ2L or mutant γ2L(P302L) subunits in HEK 293T cells and cultured mouse cortical neurons. We measured currents using whole-cell and single-channel patch clamp techniques, surface and total expression levels using surface biotinylation and Western blotting, and potential structural perturbations in mutant GABAA receptors using structural modeling...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28196855/inactivation-of-girk-channels-weakens-the-pre-and-postsynaptic-inhibitory-activity-in-dorsal-raphe-neurons
#13
Nerea Llamosas, Luisa Ugedo, Maria Torrecilla
The serotonergic tone of the dorsal raphe (DR) is regulated by 5-HT1A receptors, which negatively control serotonergic activity via the activation of G protein-coupled inwardly rectifying K(+) (GIRK) channels. In addition, DR activity is modulated by local GABAergic transmission, which is believed to play a key role in the development of mood-related disorders. Here, we sought to characterize the role of GIRK2 subunit-containing channels on the basal electrophysiological properties of DR neurons and to investigate whether the presynaptic and postsynaptic activities of 5-HT1A, GABAB, and GABAA receptors are affected by Girk2 gene deletion...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28195311/reduced-local-input-to-fast-spiking-interneurons-in-the-somatosensory-cortex-in-the-gabaa-%C3%AE-2-r43q-mouse-model-of-absence-epilepsy
#14
Stephen P Currie, Liliana L Luz, Sam A Booker, David J A Wyllie, Peter C Kind, Michael I Daw
OBJECTIVE: Absence seizures in childhood absence epilepsy are initiated in the thalamocortical (TC) system. We investigated if these seizures result from altered development of the TC system before the appearance of seizures in mice containing a point mutation in γ-aminobutyric acid A (GABAA ) receptor γ2 subunits linked to childhood absence epilepsy (R43Q). Findings from conditional mutant mice indicate that expression of normal γ2 subunits during preseizure ages protect from later seizures...
February 13, 2017: Epilepsia
https://www.readbyqxmd.com/read/28192273/gabaa-receptor-subtypes-in-the-mouse-brain-regional-mapping-and-diazepam-receptor-occupancy-by-in-vivo-18-f-flumazenil-pet
#15
Adrienne Müller Herde, Dietmar Benke, William T Ralvenius, Linjing Mu, Roger Schibli, Hanns Ulrich Zeilhofer, Stefanie D Krämer
Classical benzodiazepines, which are widely used as sedatives, anxiolytics and anticonvulsants, exert their therapeutic effects through interactions with heteropentameric GABAA receptors composed of two α, two β and one γ2 subunit. Their high affinity binding site is located at the interface between the γ2 and the adjacent α subunit. The α-subunit gene family consists of six members and receptors can be homomeric or mixed with respect to the α-subunits. Previous work has suggested that benzodiazepine binding site ligands with selectivity for individual GABAA receptor subtypes, as defined by the benzodiazepine-binding α subunit, may have fewer side effects and may even be effective in diseases, such as schizophrenia, autism or chronic pain, that do not respond well to classical benzodiazepines...
February 10, 2017: NeuroImage
https://www.readbyqxmd.com/read/28186121/astrocyte-deletion-of-bmal1-alters-daily-locomotor-activity-and-cognitive-functions-via-gaba-signalling
#16
Olga Barca-Mayo, Meritxell Pons-Espinal, Philipp Follert, Andrea Armirotti, Luca Berdondini, Davide De Pietri Tonelli
Circadian rhythms are controlled by a network of clock neurons in the central pacemaker, the suprachiasmatic nucleus (SCN). Core clock genes, such as Bmal1, are expressed in SCN neurons and in other brain cells, such as astrocytes. However, the role of astrocytic clock genes in controlling rhythmic behaviour is unknown. Here we show that ablation of Bmal1 in GLAST-positive astrocytes alters circadian locomotor behaviour and cognition in mice. Specifically, deletion of astrocytic Bmal1 has an impact on the neuronal clock through GABA signalling...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28176641/gaba-a-receptor-subtypes-implications-for-the-treatment-of-pain
#17
Bradford D Fischer
Chronic severe pain is treated most successfully with opioid analgesics, although the clinical use of these drugs is constrained by unwanted side effects, including the potential for abuse. GABAergic neurons are located in spinal nociceptive circuits suggesting that drugs with affinity at these receptors, including benzodiazepine-like drugs, may provide an alternative to opioids for the treatment of pain. However, systemically administered conventional benzodiazepines fail to produce antihyperalgesic effects, likely due to their concurrent sedative properties...
February 7, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28176165/hemodynamic-changes-associated-with-interictal-spikes-induced-by-acute-models-of-focal-epilepsy-in-rats-a-simultaneous-electrocorticography-and-near-infrared-spectroscopy-study
#18
Viktoriya Osharina, Ardalan Aarabi, Mana Manoochehri, Mahdi Mahmoudzadeh, Fabrice Wallois
Interictal spikes can be generated by blocking GABAA receptor-mediated inhibition. The nature of the hemodynamic activities associated with interictal spikes in acute models of focal epilepsy based on GABA deactivation has not been determined. We analyzed systemic changes in hemodynamic signals associated with interictal spikes generated by acute models of focal epilepsy. Simultaneous ElectroCorticoGraphy (ECoG) and Near-InfraRed Spectroscopy (NIRS) recordings were obtained in vivo from adult Sprague-Dawley rat brain during semi-periodic focal interictal spikes induced by local cortical application of low doses of Penicillin G (PG) and Bicuculline Methiodide (BM) as GABA deactivation agents...
February 7, 2017: Brain Topography
https://www.readbyqxmd.com/read/28163252/the-legacy-pesticide-dieldrin-acts-as-a-teratogen-and-alters-the-expression-of-dopamine-transporter-and-dopamine-receptor-2a-in-zebrafish-danio-rerio-embryos
#19
Kathleena I Sarty, Andrew Cowie, Christopher J Martyniuk
Dieldrin (DLD) is a lipophilic pesticide that shows environmental persistence. The objectives were to determine the effects of DLD on GABAergic and dopaminergic systems in developing zebrafish. Both chorionated and dechorionated embryos (~24h post-hatch) were exposed to a single concentration of DLD (0.347-3470μM) for 48h. Following exposure, a subset of larvae was placed into clean water for 6days (i.e. depuration phase). Chorionated embryos showed <15% mortality while dechorionated embryos showed higher mortality (>30%), suggesting that the chorion protected the embryos...
February 3, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28163104/age-dependent-regulation-of-gaba-transmission-by-kappa-opioid-receptors-in-the-basolateral-amygdala-of-sprague-dawley-rats
#20
K R Przybysz, D F Werner, M R Diaz
Anxiety disorders are one of the most common and debilitating mental illnesses worldwide. Growing evidence indicates an age-dependent rise in the incidence of anxiety disorders from adolescence through adulthood, suggestive of underlying neurodevelopmental mechanisms. Kappa opioid receptors (KORs) are known to contribute to the development and expression of anxiety; however, the functional role of KORs in the basolateral amygdala (BLA), a brain structure critical in mediating anxiety, particularly across ontogeny, are unknown...
February 3, 2017: Neuropharmacology
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