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https://www.readbyqxmd.com/read/28635080/neuroadaptations-of-presynaptic-and-postsynaptic-gabab-receptor-function-in-the-paraventricular-nucleus-in-response-to-chronic-unpredictable-stress
#1
Yonggang Gao, Jing-Jing Zhou, Yun Zhu, Li Wang, Therese A Kosten, Xiangjian Zhang, De-Pei Li
BACKGROUND: Chronic stress induces an impaired GABAA (γ-aminobutyric acid type A) receptor-mediated inhibition in the hypothalamic paraventricular nucleus (PVN). It is not clear whether GABAB receptor function is altered in chronic stress. We hypothesize that chronic stress alters GABAB receptor function in PVN corticotrophin-releasing hormone (CRH) neurons to control hypothalamus-pituitary-adrenal (HPA) axis activity. EXPERIMENTAL APPROACH: Whole cell patch-clamp recording was performed on PVN-CRH neurons expressing eGFP driven by CRH promoter in brain slices from unstressed rats and rats that had been subjected to chronic unpredictable mild stress (CUMS)...
June 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28608233/alleviation-by-gabab-receptors-of-neurotoxicity-mediated-by-mitochondrial-permeability-transition-pore-in-cultured-murine-cortical-neurons-exposed-to-n-methyl-d-aspartate
#2
Toshihiko Kinjo, Yoshino Ashida, Hiroshi Higashi, Satoshi Sugimura, Miho Washida, Hiroki Niihara, Kiyokazu Ogita, Yukio Yoneda, Nobuyuki Kuramoto
Mitochondrial permeability transition pore (PTP) is supposed to at least in part participate in molecular mechanisms underlying the neurotoxicity seen after overactivation of N-methyl-D-aspartate (NMDA) receptor (NMDAR) in neurons. In this study, we have evaluated whether activation of GABAB receptor (GABABR), which is linked to membrane G protein-coupled inwardly-rectifying K(+) ion channels (GIRKs), leads to protection of the NMDA-induced neurotoxicity in a manner relevant to mitochondrial membrane depolarization in cultured embryonic mouse cortical neurons...
June 12, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28606304/presynaptic-lrp4-promotes-synapse-number-and-function-of-excitatory-cns-neurons
#3
Timothy J Mosca, David J Luginbuhl, Irving E Wang, Liqun Luo
Precise coordination of synaptic connections ensures proper information flow within circuits. The activity of presynaptic organizing molecules signaling to downstream pathways is essential for such coordination, though such entities remain incompletely known. We show that LRP4, a conserved transmembrane protein known for its postsynaptic roles, functions presynaptically as an organizing molecule. In the Drosophila brain, LRP4 localizes to the nerve terminals at or near active zones. Loss of presynaptic LRP4 reduces excitatory (not inhibitory) synapse number, impairs active zone architecture, and abolishes olfactory attraction - the latter of which can be suppressed by reducing presynaptic GABAB receptors...
June 13, 2017: ELife
https://www.readbyqxmd.com/read/28596118/neuroprotective-role-of-gabab-receptor-modulation-against-streptozotocin-induced-behavioral-and-biochemical-abnormalities-in-rats
#4
Kushal Kumar, Harmanpreet Kaur, Rahul Deshmukh
Stimulation as well as inhibition of GABAB (Gamma amino butyric acid) receptors has been reported to show beneficial effects in Alzheimer's disease (AD). Experimental evidences suggest that the use of GABAergic agents could influence learning and memory. The present study was designed to investigate the possible role of GABAB receptors in streptozotocin (STZ)-induced behavioral and biochemical abnormalities in rats. Herein STZ was infused (3mg/kg) bilaterally on alternate days (day 1 and day 3) to produce experimental dementia in rats...
June 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28565998/gabab-receptors-mediated-tonic-inhibition-of-glutamate-release-from-a%C3%AE-fibers-in-rat-laminae-iii-iv-of-the-spinal-cord-dorsal-horn
#5
Chiara Salio, Adalberto Merighi, Rita Bardoni
Presynaptic GABAB receptors (GABABRs) are highly expressed in dorsal root ganglion neurons and spinal cord dorsal horn. GABABRs located in superficial dorsal horn play an important antinociceptive role, by acting at both pre- and postsynaptic sites. GABABRs expressed in deep dorsal horn could be involved in the processing of touch sensation and possibly in the generation of tactile allodynia in chronic pain. The objective of this study was to characterize the morphological and functional properties of GABABRs expressed on Aβ fibers projecting to lamina III/IV and to understand their role in modulating excitatory synaptic transmission...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28553835/pharmacological-manipulation-of-cortical-inhibition-in-the-dorsolateral-prefrontal-cortex
#6
Bahar Salavati, Tarek K Rajji, Reza Zomorrodi, Daniel M Blumberger, Robert Chen, Bruce G Pollock, Zafiris J Daskalakis
Cortical inhibition (CI) occurs largely through GABA receptor mediated inhibitory neurotransmission, which can be modulated by cholinergic, dopaminergic, and glutamatergic inputs. Transcranial magnetic stimulation (TMS) can be used to index CI through a paradigm known as long interval cortical inhibition (LICI). When TMS is combined with electroencephalography (EEG), LICI can index GABA receptor mediated inhibitory neurotransmission in the dorsolateral prefrontal cortex (DLPFC). We conducted a hypothesis-driven pharmacological study to assess the role of cholinergic, dopaminergic, GABAergic, and glutamatergic neurotransmission on LICI from the DLPFC using TMS-EEG...
May 29, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28536867/suppressing-effect-of-cor659-on-alcohol-sucrose-and-chocolate-self-administration-in-rats-involvement-of-the-gabab-and-cannabinoid-cb1-receptors
#7
Paola Maccioni, Giancarlo Colombo, Irene Lorrai, Alessandro Zaru, Mauro A M Carai, Gian Luigi Gessa, Antonella Brizzi, Claudia Mugnaini, Federico Corelli
RATIONALE AND OBJECTIVES: COR659 [methyl2-(4-chlorophenylcarboxamido)-4-ethyl-5-methylthiophene-3-carboxylate] is a new, positive allosteric modulator (PAM) of the GABAB receptor. This study evaluated whether COR659 shared with previously tested GABAB PAMs the capacity to reduce alcohol self-administration in rats. RESULTS: Treatment with non-sedative doses of COR659 (2.5, 5, and 10 mg/kg; i.p.) suppressed lever-responding for alcohol (15% v/v) in Sardinian alcohol-preferring (sP) rats under the fixed ratio (FR) 4 (FR4) and progressive ratio (PR) schedules of reinforcement; COR659 was more potent and effective than the reference GABAB PAM, GS39783...
May 24, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28534145/alterations-in-gene-expression-after-gamma-hydroxybutyric-acid-intake-a-pilot-study
#8
Lena-Maria Mehling, Annika Spottke, Anna Heidbreder, Peter Young, Burkhard Madea, Cornelius Hess, Cornelius Courts
Gamma-hydroxybutyric acid (GHB) acts as an agonist of the GABAB receptor, where GHB induces a depressant effect in the central nervous system. Besides its therapeutic application, GHB is also used as a date rape drug. However, the detection of GHB ingestion proves to be difficult due to its narrow detection window. The aim of this pilot study was to assess differential gene expressions after GHB intake to identify potential biomarkers for the detection of GHB intake. To this aim, alteration in gene expression of ALDH5A1, AKR7A2, EREG, and PEA15 was investigated via quantitative PCR (qPCR)...
May 22, 2017: International Journal of Legal Medicine
https://www.readbyqxmd.com/read/28533165/analgesic-conopeptides-targeting-g-protein-coupled-receptors-reduce-excitability-of-sensory-neurons
#9
REVIEW
Mahsa Sadeghi, Jeffrey R McArthur, Rocio K Finol-Urdaneta, David J Adams
Conotoxins (conopeptides) are a diverse group of peptides isolated from the venom of marine cone snails. Conus peptides modulate pain by interacting with voltage-gated ion channels and G protein-coupled receptors (GPCRs). Opiate drugs targeting GPCRs have long been used, nonetheless, many undesirable side effects associated with opiates have been observed including addiction. Consequently, alternative avenues to pain management are a largely unmet need. It has been shown that various voltage-gated calcium channels (VGCCs) respond to GPCR modulation...
May 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28510727/alternative-splicing-in-the-c-terminal-tail-of-cav2-1-is-essential-for-preventing-a-neurological-disease-in-mice
#10
Tomonori Aikawa, Takaki Watanabe, Taisuke Miyazaki, Takayasu Mikuni, Minoru Wakamori, Miyano Sakurai, Hidenori Aizawa, Nobutaka Ishizu, Masahiko Watanabe, Masanobu Kano, Hidehiro Mizusawa, Kei Watase
Alternative splicing (AS) that occurs at the final coding exon (exon 47) of the Cav2.1 voltage-gated calcium channel (VGCC) gene produces two major isoforms in the brain, MPI and MPc. These isoforms differ in their splice acceptor sites; human MPI is translated into a polyglutamine tract associated with spinocerebellar ataxia type 6 (SCA6), whereas MPc splices to an immediate stop codon, resulting in a shorter cytoplasmic tail.To gain insight into the functional role of the AS in vivo and whether modulating the splice patterns at this locus can be a potential therapeutic strategy for SCA6, here we created knockin mice that exclusively express MPc by inserting the splice-site mutation...
May 16, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28504122/gabab-receptors-and-pain
#11
REVIEW
Marzia Malcangio
Over the past three decades the research on GABAB receptor biology and pharmacology in pain processing has been a fascinating experience. Norman Bowery's fundamental discovery of the existence of the GABAB receptor has led the way to the definition of GABAB molecular mechanisms; patterns of receptor expression in the peripheral and central nervous system; GABAB modulatory functions within the pain pathways. We are now harnessing this acquired knowledge to develop innovative approaches to the therapeutic management of chronic pain through allosteric modulation of the GABAB...
May 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28491031/control-of-absence-seizures-by-the-thalamic-feed-forward-inhibition
#12
Mingming Chen, Daqing Guo, Yang Xia, Dezhong Yao
As a subtype of idiopathic generalized epilepsies, absence epilepsy is believed to be caused by pathological interactions within the corticothalamic (CT) system. Using a biophysical mean-field model of the CT system, we demonstrate here that the feed-forward inhibition (FFI) in thalamus, i.e., the pathway from the cerebral cortex (Ctx) to the thalamic reticular nucleus (TRN) and then to the specific relay nuclei (SRN) of thalamus that are also directly driven by the Ctx, may participate in controlling absence seizures...
2017: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/28469569/eliminating-absence-seizures-through-the-deep-brain-stimulation-to-thalamus-reticular-nucleus
#13
Zhihui Wang, Qingyun Wang
Deep brain stimulation (DBS) can play a crucial role in the modulation of absence seizures, yet relevant biophysical mechanisms are not completely established. In this paper, on the basis of a biophysical mean-field model, we investigate a typical absence epilepsy activity by introducing slow kinetics of GABAB receptors on thalamus reticular nucleus (TRN). We find that the region of spike and slow-wave discharges (SWDs) can be reduced greatly when we add the DBS to TRN. Furthermore, we systematically explore how the corresponding stimulation parameters including frequency, amplitude and positive input duration suppress the SWDs under certain conditions...
2017: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/28466358/differential-surface-density-and-modulatory-effects-of-presynaptic-gabab-receptors-in-hippocampal-cholecystokinin-and-parvalbumin-basket-cells
#14
Sam A Booker, Daniel Althof, Claudius E Degro, Masahiko Watanabe, Ákos Kulik, Imre Vida
The perisomatic domain of cortical neurons is under the control of two major GABAergic inhibitory interneuron types: regular-spiking cholecystokinin (CCK) basket cells (BCs) and fast-spiking parvalbumin (PV) BCs. CCK and PV BCs are different not only in their intrinsic physiological, anatomical and molecular characteristics, but also in their presynaptic modulation of their synaptic output. Most GABAergic terminals are known to contain GABAB receptors (GABABR), but their role in presynaptic inhibition and surface expression have not been comparatively characterized in the two BC types...
May 2, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28462453/preclinical-screening-for-treatments-for-infantile-spasms-in-the-multiple-hit-rat-model-of-infantile-spasms-an-update
#15
Aristea S Galanopoulou, Wenzhu B Mowrey, Wei Liu, Qianyun Li, Oleksii Shandra, Solomon L Moshé
Infantile spasms are the typical seizures of West syndrome, an infantile epileptic encephalopathy with poor outcomes. There is an increasing need to identify more effective and better tolerated treatments for infantile spasms. We have optimized the rat model of infantile spasms due to structural etiology, the multiple-hit rat model, for therapy discovery. Here, we test three compounds administered after spasms induction in the multiple hit model for efficacy and tolerability. Specifically, postnatal day 3 (PN3) male Sprague-Dawley rats were induced by right intracerebral injections of doxorubicin and lipopolysaccharide...
May 2, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28450542/neuronal-chloride-regulation-via-kcc2-is-modulated-through-a-gabab-receptor-protein-complex
#16
Rebecca Wright, Sarah E Newey, Andrei Ilie, Winnie Wefelmeyer, Joseph V Raimondo, Rachel Ginham, R A Jeffrey Mcllhinney, Colin J Akerman
GABAB receptors are G-protein-coupled receptors that mediate inhibitory synaptic actions through a series of downstream target proteins. It is increasingly appreciated that the GABAB receptor forms part of larger signaling complexes, which enable the receptor to mediate multiple different effects within neurons. Here we report that GABAB receptors can physically associate with the potassium-chloride cotransporter protein, KCC2, which sets the driving force for the chloride-permeable ionotropic GABAA receptor in mature neurons...
May 31, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28449268/ventral-but-not-dorsal-hippocampus-inactivation-impairs-reward-memory-expression-and-retrieval-in-contexts-defined-by-proximal-cues
#17
Sadia Riaz, Anett Schumacher, Seyon Sivagurunathan, Matthijs Van Der Meer, Rutsuko Ito
The hippocampus (HPC) has been widely implicated in the contextual control of appetitive and aversive conditioning. However, whole hippocampal lesions do not invariably impair all forms of contextual processing, as in the case of complex biconditional context discrimination, leading to contention over the exact nature of the contribution of the HPC in contextual processing. Moreover, the increasingly well-established functional dissociation between the dorsal (dHPC) and ventral (vHPC) subregions of the HPC has been largely overlooked in the existing literature on hippocampal-based contextual memory processing in appetitively motivated tasks...
July 2017: Hippocampus
https://www.readbyqxmd.com/read/28444246/lateral-orbitofrontal-cortical-modulation-on-medial-prefrontal-cortex-amygdala-pathway-differential-regulation-of-intra-amygdala-gabaa-and-gabab-receptors
#18
Chun-Hui Chang
Background: The basolateral complex of the amygdala receives inputs from neocortical areas, including the medial prefrontal cortex (mPFC) and lateral orbitofrontal cortex (lOFC). Earlier studies have shown that lOFC activation exerts an inhibitory gating on mPFC-amygdala information flow. Here we examined the individual role of GABAA and GABAB receptors in this process. Methods: In vivo extracellular single-unit recordings were done in anesthetized rats. We searched amygdala neurons that fire in response to mPFC activation, tested lOFC gating at different delays (lOFC-mPFC delays: 25, 50, 100, 250, 500, and 1000 ms), and examined differential contribution of GABAA and GABAB receptors with iontophoresis...
April 22, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28438833/the-g-protein-gi1-exhibits-basal-coupling-but-not-preassembly-with-g-protein-coupled-receptors
#19
Alexey Bondar, Josef Lazar
The Gi/o protein family transduces signals from a diverse group of G protein-coupled receptors (GPCRs). The observed specificity of Gi/o-GPCR coupling and the high rate of Gi/o signal transduction have been hypothesized to be enabled by the existence of stable associates between Gi/o proteins and their cognate GPCRs in the inactive state (Gi/o-GPCR preassembly). To test this hypothesis, we applied the recently developed technique of two-photon polarization microscopy (2PPM) to Gαi1 subunits labeled with fluorescent proteins and four GPCRs: the α2A-adrenergic receptor, GABAB, cannabinoid receptor type 1 (CB1R), and dopamine receptor type 2...
June 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28424564/new-developments-in-the-management-of-narcolepsy
#20
REVIEW
Vivien C Abad, Christian Guilleminault
Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%-0.18% of the US and Western European populations. Genetic predisposition is suspected because of narcolepsy's strong association with HLA DQB1*06-02, and genome-wide association studies have identified polymorphisms in T-cell receptor loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin-producing neurons; an autoimmune etiology possibly triggered by some environmental agent may precipitate hypocretin neuronal loss...
2017: Nature and Science of Sleep
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