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GABA receptor

Doodipala Samba Reddy
Neurosteroids like allopregnanolone (AP) are positive allosteric modulators of synaptic and extrasynaptic GABA-A receptors. AP and related neurosteroids exhibit a greater potency for δ-containing extrasynaptic receptors. The δGABA-A receptors, which are expressed extrasynaptically in the dentate gyrus and other regions, contribute to tonic inhibition, promoting network shunting as well as reducing seizure susceptibility. Levels of endogenous neurosteroids fluctuate with ovarian cycle. Natural and synthetic neurosteroids maximally potentiate tonic inhibition in the hippocampus and provide robust protection against a variety of limbic seizures and status epilepticus...
2018: Vitamins and Hormones
Caitlin A Wotton, Elizabeth F Quon, Ashley C Palmer, Lane K Bekar
Both serotonin (5HT) and stress exert changes in cortical inhibitory tone to shape activity of cortical networks. As astrocytes are also known to affect inhibition through established purinergic pathways, we assessed the role of GABA and purinergic pathways in rapid corticosterone (CORT) and 5HT effects on cortical inhibition. We used a paired-pulse paradigm (P1 & P2) in acutely isolated mouse brain slices to evaluate changes in cortical evoked inhibition. Normally, 5HT decreases amplitude of the first pulse P1, while increasing the amplitude of P2 (increase frequency transmission)...
March 15, 2018: Journal of Neuroendocrinology
Tao Tan, Wei Wang, Haitao Xu, Zhilin Huang, Yu Tian Wang, Zhifang Dong
Patients with autism spectrum disorder (ASD) display abnormalities in neuronal development, synaptic function and neural circuits. The imbalance of excitatory and inhibitory (E/I) synaptic transmission has been proposed to cause the main behavioral characteristics of ASD. Repetitive transcranial magnetic stimulation (rTMS) can directly or indirectly induce excitability and synaptic plasticity changes in the brain noninvasively. However, whether rTMS can ameliorate autistic-like behaviors in animal model via regulating the balance of E/I synaptic transmission is unknown...
2018: Frontiers in Cellular Neuroscience
Juan Francisco Rodríguez-Landa, Jonathan Cueto-Escobedo, Luis Ángel Flores-Aguilar, Gilberto Uriel Rosas-Sánchez, María de Jesús Rovirosa-Hernández, Francisco García-Orduña, Miguel Carro-Juárez
BACKGROUND: Montanoa frutescens and Montanoa grandiflora have been indistinctly used for centuries in traditional Mexican medicine for reproductive impairments, anxiety, and mood disorders. Preclinical studies support their aphrodisiac and anxiolytic properties, but their effects on mood are still unexplored. METHODS: The effects of 25 and 50 mg/kg of M frutescens and M grandiflora extracts were evaluated on days 1, 7, 14, 21, and 28 of treatment, and compared with fluoxetine (1 mg/kg) and Remotiv (7...
January 2018: J Evid Based Integr Med
Lei Liu, Wataru Ito, Alexei Morozov
Region and cell-type restricted expression of light-activated ion channels is the indispensable tool to study properties of synapses in specific circuits and to monitor synaptic alterations by various stimuli including neuromodulators and behaviors, both ex vivo and in vivo . These analyses require the light-activated proteins or viral vectors for their delivery that do not interfere with the phenomenon under study. Here, we report a case of such interference in which the high-level expression of channelrhodopsin-2 introduced in the somatostatin-positive GABAergic neurons of the dorsomedial prefrontal cortex by an adeno-associated virus vector weakens the presynaptic GABAb receptor-mediated suppression of GABA release...
April 2018: Neurophotonics
Alexander J Riordan, Ari W Schaler, Jenny Fried, Tracie A Paine, Janice E Thornton
The cognitive symptoms of schizophrenia are poorly understood and difficult to treat. Estrogens may mitigate these symptoms via unknown mechanisms. To examine these mechanisms, we tested whether increasing estradiol (E) or decreasing luteinizing hormone (LH) could mitigate short-term episodic memory loss in a phencyclidine (PCP) model of schizophrenia. We then assessed whether changes in cortical or hippocampal GABA may underlie these effects. Female rats were ovariectomized and injected subchronically with PCP...
February 27, 2018: Psychoneuroendocrinology
Oliver G Bosch, Fabrizio Esposito, Dario Dornbierer, Michael M Havranek, Robin von Rotz, Michael Kometer, Philipp Staempfli, Boris B Quednow, Erich Seifritz
According to the triple network hypothesis the brain is equipped with three core neurocognitive networks: the default mode (DMN), the salience (SN), and the central executive (CEN) network. Moreover, the so called dorsal nexus, has met growing interest as it is a hub region connecting these three networks. Assessment of resting-state functional connectivity (rsFC) of these networks enables the elucidation of drug-induced brain alterations. Gamma-hydroxybutyrate (GHB) is a GHB/GABA-B receptor agonist that induces a paradoxical state of mixed stimulation and sedation at moderate doses, which makes it a valuable tool to investigate neural signatures of subjective drug effects...
March 7, 2018: NeuroImage
Mana Ogawa, Toshitada Nagai, Yoshikazu Saito, Hitonari Miyaguchi, Kei Kumakura, Keiko Abe, Tomiko Asakura
Mastication enhances brain function and mental health, but little is known about the molecular mechanisms underlying the effects of mastication on neural development in early childhood. Therefore, we analysed the gene expression in juvenile neural circuits in rats fed with a soft or chow diet immediately after weaning. We observed that the gene expression patterns in the thalamus varied depending on the diet. Furthermore, gene ontology analysis revealed that two terms were significantly enhanced: chemical synaptic transmission and positive regulation of dendritic spine morphogenesis...
March 7, 2018: Biochemical and Biophysical Research Communications
John E Casida
Insecticide radioligands allow the direct recognition and analysis of the targets and mechanisms of toxic action critical to effective and safe pest control. These radioligands are either the insecticides themselves or analogs that bind at the same or coupled sites. Preferred radioligands and their targets, often in both insects and mammals, are trioxabicyclooctanes for the GABA receptor, avermectin for the Glutamate receptor, imidacloprid for the nicotinic receptor, ryanodine and chlorantraniliprole for the ryanodine receptor, and rotenone or pyridaben for NADH+ ubiquinone oxidoreductase...
March 9, 2018: Journal of Agricultural and Food Chemistry
Warren Pan, Jessica M Adams, Margaret B Allison, Christa Patterson, Jonathan N Flak, Justin Jones, Garth Strohbehn, James Trevaskis, Christopher J Rhodes, David P Olson, Martin G Myers
The adipocyte-derived hormone, leptin, acts via its receptor (LepRb) on central nervous system neurons to communicate the repletion of long-term energy stores, to decrease food intake and promote energy expenditure. We generated mice that express cre recombinase from the calcitonin receptor (Calcr) locus (Calcrcre mice) to study Calcr-expressing LepRb (LepRbCalcr) neurons, which reside predominantly in the arcuate nucleus (ARC). Calcrcre-mediated ablation of LepRb in LepRbCalcrKO mice caused hyperphagic obesity...
March 7, 2018: Endocrinology
Paula P Perissinotti, María Celeste Rivero-Echeto, Edgar Garcia-Rill, Verónica Bisagno, Francisco J Urbano
Leptin is an adipose-derived hormone that controls appetite and energy expenditure. Leptin receptors are expressed on extra-hypothalamic ventrobasal (VB) and reticular thalamic (RTN) nuclei from embryonic stages. Here, we studied the effects of pressure-puff, local application of leptin on both synaptic transmission and action potential properties of thalamic neurons in thalamocortical slices. We used whole-cell patch-clamp recordings of thalamocortical VB neurons from wild-type (WT) and leptin-deficient obese (ob/ob) mice...
March 8, 2018: Brain Structure & Function
John Peyton Bohnsack, Benjamin A Hughes, Todd K O'Buckley, Kamyra Edokpolor, Joyce Besheer, A Leslie Morrow
Alcohol use disorders are chronic debilitating diseases characterized by severe withdrawal symptoms that contribute to morbidity and relapse. GABAA receptor (GABAA R) adaptations have long been implicated in the chronic effects of alcohol and contribute to many withdrawal symptoms associated with alcohol dependence. In rodents, GABAA R hypofunction results from decreases in Gabra1 expression, although the underlying mechanism controlling Gabra1 expression after chronic ethanol exposure is still unknown. We found that chronic ethanol exposure using either ethanol gavage or two-bottle choice voluntary access paradigms decreased Gabra1 expression and increased Hdac2 and Hdac3 expression...
February 27, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Lih-Chu Chiou, Hsin-Jung Lee, Margot Ernst, Wei-Jan Huang, Jui-Feng Chou, Hon-Lie Chen, Akihiro Mouri, Liang-Chieh Chen, Marco Treven, Takayoshi Mamiya, Pi-Chuan Fan, Daniel E Knutson, Chris Witzigmann, James Cook, Werner Sieghart, Toshitaka Nabeshima
BACKGROUND AND PURPOSE: The pathophysiological role of α6 subunit-containing GABAA receptors (α6GABAA Rs), which are mainly expressed in cerebellar granule cells, remains unclear. Recently, we demonstrated that hispidulin, a flavonoid isolated from a local herb that remitted a patient's intractable motor tics, attenuated methamphetamine-induced hyperlocomotion in mice as a positive allosteric modulator (PAM) of cerebellar α6GABAA Rs. Here, using hispidulin and a selective α6GABAA R PAM, the pyrazoloquinolinone Compound 6, we revealed an unprecedented role of cerebellar α6GABAA Rs in disrupted prepulse inhibition (PPI), which reflects sensorimotor gating deficits manifested in several neuropsychiatric disorders...
March 8, 2018: British Journal of Pharmacology
Panos Zanos, Scott M Thompson, Ronald S Duman, Carlos A Zarate, Todd D Gould
Traditional pharmacological treatments for depression have a delayed therapeutic onset, ranging from several weeks to months, and there is a high percentage of individuals who never respond to treatment. In contrast, ketamine produces rapid-onset antidepressant, anti-suicidal, and anti-anhedonic actions following a single administration to patients with depression. Proposed mechanisms of the antidepressant action of ketamine include N-methyl-D-aspartate receptor (NMDAR) modulation, gamma aminobutyric acid (GABA)-ergic interneuron disinhibition, and direct actions of its hydroxynorketamine (HNK) metabolites...
March 7, 2018: CNS Drugs
Kyle J Brymer, Erin Y Fenton, Lisa E Kalynchuk, Hector J Caruncho
Depression is a serious psychiatric disorder frequently comorbid with autoimmune disorders. Previous work in our lab has demonstrated that repeated corticosterone (CORT) injections in rats reliably increase depressive-like behavior, impair hippocampal-dependent memory, reduce the number and complexity of adult-generated neurons in the dentate gyrus, decrease hippocampal reelin expression, and alter markers of GABAergic function. We hypothesized that peripheral injections of the TNF-α inhibitor etanercept could exert antidepressant effects through a restoration of many of these neurobiological changes...
2018: Frontiers in Pharmacology
Kiyoto Kanbara, Yoshinori Otsuki, Masahito Watanabe, Syunichi Yokoe, Yoshiaki Mori, Michio Asahi, Masashi Neo
BACKGROUND: High-grade chondrosarcoma, which has a high incidence of local recurrence and pulmonary metastasis despite surgical resection, is associated with poor prognosis. Therefore, new and effective adjuvant therapies are urgently required for this disease. Gamma-aminobutyric acid (GABA), which acts as a neurotrophic factor during nervous system development, is related to the proliferation and migration of certain cancer cells. The GABAergic system, which is composed of GABA, the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD), and GABA receptors, has an important function in nerve growth and development of neural crest...
March 7, 2018: BMC Cancer
Sumit Jamwal, Puneet Kumar
Alteration in neurotransmitters signaling in basal ganglia has been consistently shown to significantly contribute to the pathophysiological basis of Parkinson's disease and Huntington's disease. Dopamine is important neurotransmitter which play critical role in coordinated body movements. Alteration in level of brain dopamine and receptor radically contribute to irregular movements, glutamate mediated excitotoxic neuronal death and further leads to imbalance in the levels of other neurotransmitters viz. GABA, adenosine, acetylcholine and endocannabinoids...
March 1, 2018: Current Neuropharmacology
Bojana Kokinovic, Paolo Medini
Recovery after stroke is mediated by plastic changes largely occurring in the lesion periphery. However, little is known on the microcircuit changes underlying recovery, at which extent perilesional plasticity occurs at synaptic input vs. spike output level, and on the connectivity behind such synaptic plasticity. We combined intrinsic imaging with extra- and intra-cellular recordings and pharmacological inactivation in a focal stroke in mouse somatosensory cortex (S1). In vivo whole-cell recordings in hindlimb S1 (hS1) showed synaptic responses also to forelimb stimulation in controls, and such responses were abolished by stroke of neighboring forelimb area (fS1), suggesting that in normal conditions they originate via horizontal connections from neighboring fS1...
March 5, 2018: Journal of Physiology
Kellie A Woll, Xiaojuan Zhou, Natarajan V Bhanu, Benjamin A Garcia, Manuel Covarrubias, Keith W Miller, Roderic G Eckenhoff
Most general anesthetics enhance GABA type A (GABAA ) receptor activity at clinically relevant concentrations. Sites of action of volatile anesthetics on the GABAA receptor remain unknown, whereas sites of action of many intravenous anesthetics have been identified in GABAA receptors by using photolabeling. Here, we used photoactivatable analogs of isoflurane (AziISO) and sevoflurane (AziSEVO) to locate their sites on α1 β3 γ2L and α1 β3 GABAA receptors. As with isoflurane and sevoflurane, AziISO and AziSEVO enhanced the currents elicited by GABA...
March 5, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Sima Dameni, Atousa Janzadeh, Mahmoud Yousefifard, Farinaz Nasirinezhad
BACKGROUND: and aim: Irisin is a new myokine that is secreted by myocytes during exercise, and plays a role in creating the beneficial effects of exercise on metabolism. Considering the benefits of exercise in reducing pain, this study was carried out to determine the probable effect of irisin on neuropathic pain in the chronic constriction injury (CCI) model in male rats. METHODS: To induce neuropathic pain CCI model was used. Animals were divided into groups of control, CCI, sham, CCI + vehicle, and CCI + irisin...
February 28, 2018: Journal of Chemical Neuroanatomy
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