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https://www.readbyqxmd.com/read/29218727/gabaa-and-gabab-receptor-subunit-localisation-on-neurochemically-identified-neurons-of-the-human-subthalamic-nucleus
#1
Xi Hua Wu, Jennifer Junru Song, Richard Lewis Maxwell Faull, Henry John Waldvogel
The subthalamic nucleus (STN) is a critical excitatory signalling centre within the basal ganglia circuitry. The activity of subthalamic neurons is tightly controlled by upstream inhibitory signalling centres in the basal ganglia. In this study, we used immunohistochemical techniques to firstly, visualise and quantify the STN neurochemical organisation based on neuronal markers including parvalbumin (PV), calretinin (CR), SMI-32 and GAD65/67 . Secondly, we characterised the detailed regional, cellular and subcellular expression of GABAA (α1 , α2 , α3 , β2/3 and γ2 ) and GABAB (R1 and R2) receptor subunits within the normal human STN...
December 8, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/29217836/drug-development-for-neurodevelopmental-disorders-lessons-learned-from-fragile-x-syndrome
#2
REVIEW
Elizabeth M Berry-Kravis, Lothar Lindemann, Aia E Jønch, George Apostol, Mark F Bear, Randall L Carpenter, Jacqueline N Crawley, Aurore Curie, Vincent Des Portes, Farah Hossain, Fabrizio Gasparini, Baltazar Gomez-Mancilla, David Hessl, Eva Loth, Sebastian H Scharf, Paul P Wang, Florian Von Raison, Randi Hagerman, Will Spooren, Sébastien Jacquemont
Neurodevelopmental disorders such as fragile X syndrome (FXS) result in lifelong cognitive and behavioural deficits and represent a major public health burden. FXS is the most frequent monogenic form of intellectual disability and autism, and the underlying pathophysiology linked to its causal gene, FMR1, has been the focus of intense research. Key alterations in synaptic function thought to underlie this neurodevelopmental disorder have been characterized and rescued in animal models of FXS using genetic and pharmacological approaches...
December 8, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29214392/modulation-of-specific-inhibitory-networks-in-fatigued-locomotor-muscles-of-healthy-males
#3
Stuart Goodall, Glyn Howatson, Kevin Thomas
Reduced maximal force capability of skeletal muscle, as a consequence of exercise, can be due to peripheral or central fatigue mechanisms. In upper-limb muscles, neuromuscular fatigue is concurrent with reduced corticospinal excitability and increased inhibition (lengthened corticospinal silent period [CSP]; reduced short-interval intracortical inhibition [SICI] ratio). However, it is unclear whether these adjustments occur in response to fatiguing exercise of locomotor muscles. This study examined the effect of fatiguing, maximal, knee-extensor exercise on motor cortical excitability and inhibition...
December 6, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/29212923/response-inhibition-activates-distinct-motor-cortical-inhibitory-processes
#4
John Cirillo, Matthew J Cowie, Hayley J MacDonald, Winston D Byblow
We routinely cancel pre-planned movements that are no longer required. If stopping is forewarned, proactive processes are engaged to selectively decrease motor cortex excitability. However, without advance information there is a non-selective reduction in motor cortical excitability. Here we examine modulation of human primary motor cortex inhibitory networks during response inhibition tasks with informative and uninformative cues using paired-pulse transcranial magnetic stimulation. Long- and short-interval intracortical inhibition (LICI and SICI), indicative of GABAB- and GABAA-receptor mediated inhibition respectively, were examined from motor evoked potentials obtained in task-relevant and task-irrelevant hand muscles when response inhibition was preceded by informative and uninformative cues...
December 6, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29195839/the-ventromedial-hypothalamic-nucleus-plays-an-important-role-in-anxiolytic-like-effect-of-neuropeptide-s
#5
Jin Hong Jiang, Ya Li Peng, Pei Jiang Zhang, Hong Xiang Xue, Zhen He, Xue Ya Liang, M Chang
Neuropeptide S (NPS), the endogenous neuropeptide ligand of NPSR, has been reported to regulate anxiety-related behavior involved in multiple brain regions, including amygdale, locus coeruleus and Barrington's nucleus. However, little research has been conducted on the anxiolytic-like behaviors of NPS on the hypothalamus, which was an important area in defensive behavior. Here, we investigated a role of hypothalamus in anxiolytic-like behaviors of NPS. We found that NPSR protein of mouse distributed mainly in the ventromedial hypothalamus (VMH)...
November 7, 2017: Neuropeptides
https://www.readbyqxmd.com/read/29194563/cyclic-analogues-of-%C3%AE-conotoxin-vc1-1-inhibit-colonic-nociceptors-and-provide-analgesia-in-a-mouse-model-of-chronic-abdominal-pain
#6
Joel Castro, Luke Grundy, Annemie Deiteren, Andrea M Harrington, Tracey O'Donnell, Jessica Maddern, Jessi Moore, Sonia Garcia-Caraballo, Grigori Y Rychkov, Rilei Yu, Quentin Kaas, David J Craik, David J Adams, Stuart M Brierley
BACKGROUND AND PURPOSE: Patients with Irritable Bowel Syndrome suffer from chronic visceral pain (CVP); however, limited analgesic therapeutic options are currently available. We have shown that α-conotoxin Vc1.1-induced activation of GABAB receptors on the peripheral endings of colonic afferents reduces nociceptive signalling from the viscera. However, the analgesic efficacy of more stable, cyclized versions of Vc1.1 on CVP remains to be determined. EXPERIMENTAL APPROACH: Using ex vivo colonic afferent preparations, we determined the inhibitory actions of cyclized Vc1...
November 30, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29189554/paraneoplastic-lambert-eaton-myasthenic-syndrome-with-limbic-encephalitis-clinical-correlation-with-the-coexistence-of-anti-vgcc-and-anti-gabab-receptor-antibodies
#7
Jonathan J Cho, James P Wymer
OBJECTIVE: To characterize Lambert-Eaton myasthenic syndrome and limbic encephalitis with coexistent voltage-gated calcium channel (VGCC) antibody and γ-aminobutyric acid (GABA) B receptor antibody. METHODS: Case study. RESULTS: A 57-year-old man presented with 6 months of weakness, unsteadiness, and vision difficulties. Examination revealed proximal weakness and diminished reflexes. Electrodiagnostic study revealed low-amplitude motor potentials and facilitation on high-frequency stimulation...
December 2017: Journal of Clinical Neuromuscular Disease
https://www.readbyqxmd.com/read/29177691/differential-association-of-gabab-receptors-with-their-effector-ion-channels-in-purkinje-cells
#8
Rafael Luján, Carolina Aguado, Francisco Ciruela, Javier Cózar, David Kleindienst, Luis de la Ossa, Bernhard Bettler, Kevin Wickman, Masahiko Watanabe, Ryuichi Shigemoto, Yugo Fukazawa
Metabotropic GABAB receptors mediate slow inhibitory effects presynaptically and postsynaptically through the modulation of different effector signalling pathways. Here, we analysed the distribution of GABAB receptors using highly sensitive SDS-digested freeze-fracture replica labelling in mouse cerebellar Purkinje cells. Immunoreactivity for GABAB1 was observed on presynaptic and, more abundantly, on postsynaptic compartments, showing both scattered and clustered distribution patterns. Quantitative analysis of immunoparticles revealed a somato-dendritic gradient, with the density of immunoparticles increasing 26-fold from somata to dendritic spines...
November 25, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29176000/effects-of-gabab-receptor-activation-on-spatial-cognitive-function-and-hippocampal-neurons-in-rat-models-of-type-2-diabetes-mellitus
#9
Xiao-Jun Cai, Lei Wang, Chun-Mei Hu
This study was conducted with the aim being to investigate the effect GABAB receptor activation plays on spatial cognitive function and hippocampal neurons found in the rat models of type 2 diabetes mellitus (T2DM). T2DM rat models were then established, randomized, and subsequently assigned into normal control (NC), T2DM, T2DM + chemical grade propylene (CGP), T2DM + baclofen, and T2DM + CGP + baclofen groups. T2DM rats' weight and blood sugar concentrations were monitored. The DMS-2 Morris water maze testing system was performed in order to figure out the spatial cognitive function of these rats...
November 24, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29171922/less-means-more-the-magnitude-of-synaptic-plasticity-along-the-hippocampal-dorso-ventral-axis-is-inversely-related-to-the-expression-levels-of-plasticity-related-neurotransmitter-receptors
#10
Valentyna Dubovyk, Denise Manahan-Vaughan
The dorsoventral axis of the hippocampus exhibits functional differentiations with regard to (spatial Vs emotional learning) and information retention (rapid encoding Vs long-term storage), as well as its sensitivity to neuromodulation and information received from extrahippocampal structures. The mechanisms that underlie these differentiations remain unclear. Here, we explored neurotransmitter receptor expression along the dorsoventral hippocampal axis and compared hippocampal synaptic plasticity in the CA1 region of the dorsal (DH), intermediate (IH) and ventral hippocampi (VH)...
November 24, 2017: Hippocampus
https://www.readbyqxmd.com/read/29166136/the-gamma-aminobutyric-acid-b-receptor-gabab-encephalitis-clinical-manifestations-and-response-to-immunotherapy
#11
Junzhao Cui, Hui Bu, Junying He, Zeyan Zhao, Weixin Han, Ruiping Gao, Xiaoqing Li, Qing Li, Xiaosu Guo, Yueli Zou
PURPOSE: We report 11 patients diagnosed with GABAB receptor (GABABR) antibodies encephalitis in China and aim to analyse the clinical characteristics, laboratory and imaging findings, therapeutic modalities and outcomes. METHODS: Clinical data from patients diagnosed with anti-GABAB receptor encephalitis in the Second Affiliated Hospital of Hebei Medical University from February 2016 to October 2016 January were retrospectively collected and evaluated. RESULTS: Seven of the eleven patients were males, and a mean age at presentation of 63 years (range: 47-79 years)...
November 22, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/29163811/impaired-gabab-mediated-presynaptic-inhibition-increases-excitatory-strength-and-alters-short-term-plasticity-in-synapsin-knockout-mice
#12
Pierluigi Valente, Pasqualina Farisello, Flavia Valtorta, Pietro Baldelli, Fabio Benfenati
Synapsins are a family of synaptic vesicle phosphoproteins regulating synaptic transmission and plasticity. SYN1/2 genes are major epilepsy susceptibility genes in humans. Consistently, synapsin I/II/III triple knockout (TKO) mice are epileptic and exhibit severe impairments in phasic and tonic GABAergic inhibition that precede the appearance of the epileptic phenotype. These changes are associated with an increased strength of excitatory transmission that has never been mechanistically investigated. Here, we observed that an identical effect in excitatory transmission could be induced in wild-type (WT) Schaffer collateral-CA1 pyramidal cell synapses by blockade of GABAB receptors (GABABRs)...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29143124/the-effect-of-inhibition-on-stimulus-specific-adaptation-in-the-inferior-colliculus
#13
Yaneri A Ayala, Manuel S Malmierca
The inferior colliculus is a center of convergence for inhibitory and excitatory synaptic inputs that may be activated simultaneously by sound stimulation. Stimulus repetition may generate response habituation by changing the efficacy of neuron's synaptic inputs. Specialized IC neurons reduce their response to repetitive tones, but restore their firing when a different and infrequent tone occurs, a phenomenon known as stimulus specific adaptation. Here, using the microiontophoresis technique, we determined the role of GABAA-, GABAB-, and glycinergic receptors in stimulus-specific adaptation (SSA)...
November 15, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29142291/resveratrol-modulates-cocaine-induced-inhibitory-synaptic-plasticity-in-vta-dopamine-neurons-by-inhibiting-phosphodiesterases-pdes
#14
Yan Li, Laikang Yu, Li Zhao, Fanxing Zeng, Qing-Song Liu
Resveratrol is a natural phytoalexin synthesized by plants, including grapes. It displays a wide range of neuroprotective benefits associated with anti-aging. Recent studies have shown that resveratrol regulates dopaminergic transmission and behavioral effects of drugs of abuse. The goal of the present study is to investigate whether and how resveratrol alters basal inhibitory synaptic transmission and cocaine-induced inhibitory synaptic plasticity in dopamine neurons of the ventral tegmental area (VTA). We report that resveratrol elevated cAMP levels by itself and further potentiated a forskolin-induced increase in cAMP levels in midbrain slices, consistent with reported effects of inhibition of phosphodiesterases (PDEs)...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137473/effect-of-short-and-long-term-administration-of-baclofen-on-spatial-learning-and-memory-in-rats
#15
M Holajova, M Franek
Baclofen is the only clinically available metabotropic GABAB receptor agonist. In our experiment, we tested the hypothesis that long-term baclofen administration can impair learning and memory in rats. The experiment consisted of three parts. In the first part of the study the drug was administered simultaneously with the beginning of the behavioral tests. In the second and third part of the experiment baclofen was administered daily for 14 days and for one month before the tests. In each part of the experiment, adult rats were randomly divided into four treatment groups...
November 10, 2017: Physiological Research
https://www.readbyqxmd.com/read/29131436/gabab-receptors-in-neocortical-and-hippocampal-pyramidal-neurons-are-coupled-to-different-potassium-channels
#16
Jean-Didier Breton, Greg J Stuart
Classically, GABAB receptors are thought to regulate neuronal excitability via G-protein coupled inwardly rectifying potassium (GIRK) channels. Recent data, however, indicates that GABAB receptors can also activate two-pore domain potassium channels. Here, we investigate which potassium channels are coupled to GABAB receptors in rat neocortical layer 5 and hippocampal CA1 pyramidal neurons. Bath application of the non-specific GIRK channel blocker barium (200 μM) abolished outward currents evoked by GABAB receptors in CA1 pyramidal, but only partially blocked GABAB responses in layer 5 neurons...
November 13, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29115173/role-of-gabab-receptors-and-p38mapk-nf-%C3%AE%C2%BAb-pathway-in-paclitaxel-induced-apoptosis-of-hippocampal-neurons
#17
Zhao Li, Peng Liu, Hailin Zhang, Shuang Zhao, Zi Jin, Rui Li, Yuexian Guo, Xiuli Wang
CONTEXT: The effects of the anticancer drug paclitaxel on learning and memory are rarely studied. OBJECTIVE: This study investigated changes in GABAB receptor expression during paclitaxel-induced apoptosis of hippocampal neurons and the role of the p38MAPK/NF-κB pathway in this process. MATERIALS AND METHODS: Hippocampal neurons isolated from neonatal Sprague-Dawley rats were divided into six groups: Control (C), SB (10 µL of 10-µmol/L SB203580), SN (53 µg/mL SN50), N (1 µmol/L paclitaxel), SB + N (10 µmol/L SB203580 + 1 µmol/L paclitaxel) and SN + N (53 µg/mL SN50 + 1 µmol/L paclitaxel)...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/29114105/neuregulin-3-signaling-mediates-nicotine-dependent-synaptic-plasticity-in-the-orbitofrontal-cortex-and-cognition
#18
Luyi Zhou, Miranda L Fisher, Robert D Cole, Thomas J Gould, Vinay Parikh, Pavel I Ortinski, Jill R Turner
Neuregulin 3 (NRG3) and ErbB4 have been linked to nicotine addiction; however, the neuronal mechanisms and behavioral consequences of NRG3-ErbB4 sensitivity to nicotine remain elusive. Recent literature suggests that relapse to smoking is due to a lack of impulsive control, which is thought to be due to altered functioning within the orbitofrontal cortex (OFC). Therefore, we examined circuitry changes within this structure following nicotine application. We report that nicotine controls synaptic plasticity in the OFC through NRG3/ErbB4-dependent regulation of GABAergic inhibition...
November 7, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29111036/gabab-receptor-ligand-directed-trimethyl-chitosan-tripolyphosphate-nanoparticles-and-their-pmdi-formulation-for-survivin-sirna-pulmonary-delivery
#19
Suhui Ni, Yun Liu, Yue Tang, Jing Chen, Shuhan Li, Ji Pu, Lidong Han
The effect of gene silencing by survivin siRNA (siSurvivin) on the proliferation and apoptosis of lung tumor has been attracted more interest. GABAB receptor ligand-directed nanoparticles consisting of baclofen functionalized trimethyl chitosan (Bac-TMC) as polymeric carriers, tripolyphosphate (TPP) as ionic crosslinker, and siSurvivin as therapeutic genes, were designed to enhance the survivin gene silencing. GABAB receptor agonist baclofen (Bac) was initially introduced into TMC as a novel ligand. This Bac-TMC/TPP nanoparticles increased the uptake of survivin siRNA through the interaction with GABAB receptor, further resulted in efficient cell apoptosis and gene silencing...
January 1, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29106983/gabab-receptor-subtypes-differentially-regulate-thalamic-spindle-oscillations
#20
REVIEW
Daniel Ulrich, Txomin Lalanne, Martin Gassmann, Bernhard Bettler
Following the discovery of GABAB receptors by Norman Bowery and colleagues, cloning and biochemical efforts revealed that GABAB receptors assemble multi-subunit complexes composed of principal and auxiliary subunits. The principal receptor subunits GABAB1a, GABAB1b and GABAB2 form two heterodimeric GABAB(1a,2) and GABAB(1b,2) receptors that can associate with tetramers of auxiliary KCTD (K(+) channel tetramerization domain) subunits. Experiments with subunit knock-out mice revealed that GABAB(1b,2) receptors activate slow inhibitory postsynaptic currents (sIPSCs) while GABAB(1a,2) receptors function as heteroreceptors and inhibit glutamate release...
October 26, 2017: Neuropharmacology
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