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https://www.readbyqxmd.com/read/29028808/functional-characterization-of-gabaa-receptor-mediated-modulation-of-cortical-neuron-network-activity-in-microelectrode-array-recordings
#1
Benjamin M Bader, Anne Steder, Anders Bue Klein, Bente Frølund, Olaf H U Schroeder, Anders A Jensen
The numerous γ-aminobutyric acid type A receptor (GABAAR) subtypes are differentially expressed and mediate distinct functions at neuronal level. In this study we have investigated GABAAR-mediated modulation of the spontaneous activity patterns of primary neuronal networks from murine frontal cortex by characterizing the effects induced by a wide selection of pharmacological tools at a plethora of activity parameters in microelectrode array (MEA) recordings. The basic characteristics of the primary cortical neurons used in the recordings were studied in some detail, and the expression levels of various GABAAR subunits were investigated by western blotting and RT-qPCR...
2017: PloS One
https://www.readbyqxmd.com/read/28988523/immunopathology-in-drug-resistant-mesial-temporal-lobe-epilepsy-with-different-types-of-hippocampal-sclerosis
#2
F Irsel Tezer, Aysegul Firat, Erdem Tuzun, Isik Unal, Figen Soylemezoglu, Burcak Bilginer, Figen Kaymaz, Kader K Oguz, Serap Saygi
PURPOSE: There is evidence that autoimmunity has a specific role in temporal lobe seizures of limbic encephalitis patients. Our aim in this study was to investigate any histopathological clues of autoimmune process in refractory temporal lobe epilepsy (TLE) patients with different pathologically proven hippocampal sclerosis (HS) types. METHODS: 22 patients who had undergone to epilepsy surgery due to mesial TLE-HS were included. The sera of patients are tested for neuronal antibodies to NMDAR, LGI1, CASPR2, AMPAR, GABABR and GAD...
October 7, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/28983255/the-regulatory-effects-of-lateral-hypothalamus-area-gabab-receptor-on-gastric-ischemia-reperfusion-injury-in-rats
#3
Lin Gao, Huiru Zhao, Tao Zhu, Yeliu Liu, Li Hu, Zhenguo Liu, Hai Huang, Fuxue Chen, Zhenxu Deng, Dechang Chu, Dongshu Du
HIGHLIGHTS The aim of the research was to determine the functional effects and molecular mechanisms of GABAB receptor on ischemia reperfusion-induced gastric injury in rats.The lateral hypothalamus area GABAB receptor attenuated the ischemia reperfusion-induced gastric injury by up-regulating the production of GABA, GABABR, and down-regulating P-GABABR in the brain.This work would provide a new therapeutic strategy for acute gastric injury. Gastric ischemia-reperfusion (GI-R) injury progression is largely associated with excessive activation of the greater splanchnic nerve (GSN)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28974152/encephalitis-with-antibodies-against-the-gabab-receptor-seizures-as-the-most-common-presentation-at-admission
#4
Xueping Chen, Fan Liu, Jin-Mei Li, Xiao-Qi Xie, Qiong Wang, Dong Zhou, Huifang Shang
OBJECTIVE: Autoimmune encephalitis associated with antibodies against gamma-aminobutyric-acid B receptor (GABABR) has not been described in detail in Chinese patients. METHODS: Patients with anti-GABABR encephalitis treated between January 2013 and December 2015 were analyzed in terms of clinical characteristics, laboratory findings, tumor presence, autoantibody patterns, treatment response and outcomes. RESULTS: Eleven patients were identified (male, N = 8; female, N = 3), with the median age of 51 years...
November 2017: Neurological Research
https://www.readbyqxmd.com/read/28966979/developmental-disruption-of-gabaar-meditated-inhibition-in-cntnap2-ko-mice
#5
Morgan S Bridi, Su Mi Park, Shiyong Huang
GABA released from presynaptic sites induces short-lived phasic inhibition mediated by synaptic GABAA receptors (GABAARs) and longer-duration tonic inhibition mediated by extrasynaptic GABAA or GABAB receptors (GABABRs). A number of studies have found that contactin-associated protein 2 (Cntnap2) knockout (KO) mice, a well-established mouse model of autism, exhibit reduced interneuron numbers and aberrant phasic inhibition. However, little is known about whether tonic inhibition is disrupted in Cntnap2 KO mice and when the disruption of inhibition begins to occur during postnatal development...
September 2017: ENeuro
https://www.readbyqxmd.com/read/28878050/antibody-associated-cns-syndromes-without-signs-of-inflammation-in-the-elderly
#6
Domingo Escudero, Mar Guasp, Helena Ariño, Carles Gaig, Eugenia Martínez-Hernández, Josep Dalmau, Francesc Graus
OBJECTIVE: To report the CNS syndromes of patients ≥60 years of age with antibodies against neuronal surface antigens but no evidence of brain MRI and CSF inflammatory changes. METHODS: This was a retrospective clinical analysis of patients with antibodies against neuronal surface antigens who fulfilled 3 criteria: age ≥60 years, no inflammatory abnormalities in brain MRI, and no CSF pleocytosis. Antibodies were determined with reported techniques. RESULTS: Among 155 patients ≥60 years of age with neurologic syndromes related to antibodies against neuronal surface antigens, 35 (22...
October 3, 2017: Neurology
https://www.readbyqxmd.com/read/28800869/the-role-of-ca3-gabab-receptors-on-anxiolytic-like-behaviors-and-avoidance-memory-deficit-induced-by-d-ap5-with-respect-to-ca-2-ions
#7
Shahram Zarrabian, Mohammad Nasehi, Maryam Farrahizadeh, Mohammad-Reza Zarrindast
Glutamatergic and GABAergic systems play key roles in the hippocampus and affect the pathogenesis of anxiety- and memory-related processes. Some investigations have assessed the role of balancing the function of these two systems in different areas of the central nervous system (CNS) as an approach to manage the related disorders. We investigated the anxiety and avoidance memory states using the test-retest protocol in the elevated plus maze to understand the role of GABAB receptors (GABABRs) in relation to the NMDA receptor blockade by D-AP5 (an NMDA receptor antagonist)...
October 3, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28713569/kctd12-modulation-of-gaba-b-receptor-function
#8
Melody Li, Carol J Milligan, Haiyan Wang, Andrew Walker, Leonid Churilov, Andrew J Lawrence, Christopher A Reid, Seth C Hopkins, Steven Petrou
The molecular composition and functional diversity of native GABAB receptors (GABABR) are still poorly understood, thus hindering development of selective GABABR ligands. Potassium channel tetramerization domain-containing protein (KCTD) 12 is a GABABR auxiliary subunit and mouse KCTD12 can alter GABABR function. In this study, we sought to characterize the effects of human KCTD12 on GABABR kinetics and pharmacology, using an automated electrophysiological assay. Seizure susceptibility and ethanol consumption were also investigated in a KCTD12 knockout mouse model...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28642282/kappa-opioid-receptors-mediate-heterosynaptic-suppression-of-hippocampal-inputs-in-the-rat-ventral-striatum
#9
Julie M Brooks, Patricio O'Donnell
Kappa opioid receptors (KORs) are highly enriched within the ventral striatum (VS) and are thought to modulate striatal neurotransmission. This includes presynaptic inhibition of local glutamatergic release from excitatory inputs to the VS. However, it is not known which inputs drive this modulation and what impact they have on the local circuit dynamics within the VS. Individual medium spiny neurons (MSNs) within the VS serve as a site of convergence for glutamatergic inputs arising from the PFC and limbic regions, such as the hippocampus (HP)...
July 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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
#10
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/28596118/neuroprotective-role-of-gabab-receptor-modulation-against-streptozotocin-induced-behavioral-and-biochemical-abnormalities-in-rats
#11
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
#12
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/28466358/differential-surface-density-and-modulatory-effects-of-presynaptic-gabab-receptors-in-hippocampal-cholecystokinin-and-parvalbumin-basket-cells
#13
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/28450542/neuronal-chloride-regulation-via-kcc2-is-modulated-through-a-gabab-receptor-protein-complex
#14
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/28424220/gababr-induced-egfr-transactivation-promotes-migration-of-human-prostate-cancer-cells
#15
Shuai Xia, Cong He, Yini Zhu, Suyun Wang, Huiping Li, Zhongling Zhang, Xinnong Jiang, Jianfeng Liu
G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) act in concert to regulate cell growth, proliferation, survival, and migration. Metabotropic GABAB receptor (GABABR) is the GPCR for the main inhibitory neurotransmitter GABA in the central nervous system. Increased expression of GABABR has been detected in human cancer tissues and cancer cell lines, but the role of GABABR in these cells is controversial and the underlying mechanism remains poorly understood. Here, we investigated whether GABABR hijacks RTK signaling to modulate the fates of human prostate cancer cells...
September 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28416021/effects-of-gabab-receptors-in-the-insula-on-recognition-memory-observed-with-intellicage
#16
Nan Wu, Feng Wang, Zhe Jin, Zhen Zhang, Lian-Kun Wang, Chun Zhang, Tao Sun
BACKGROUND: Insular function has gradually become a topic of intense study in cognitive research. Recognition memory is a commonly studied type of memory in memory research. GABABR has been shown to be closely related to memory formation. In the present study, we used intellicage, which is a new intelligent behavioural test system, and a bilateral drug microinjection technique to inject into the bilateral insula, to examine the relationship between GABABR and recognition memory. METHODS: Male Sprague-Dawley rats were randomly divided into control, Sham, Nacl, baclofen and CGP35348 groups...
April 17, 2017: Behavioral and Brain Functions: BBF
https://www.readbyqxmd.com/read/28382542/kk-92a-a-novel-gabab-receptor-positive-allosteric-modulator-attenuates-nicotine-self-administration-and-cue-induced-nicotine-seeking-in-rats
#17
Xia Li, Emmanuel Sturchler, Katarzyna Kaczanowska, Michael Cameron, M G Finn, Patrick Griffin, Patricia McDonald, Athina Markou
RATIONALE: GABAB receptors (GABABR) play a critical role in GABAergic neurotransmission in the brain and are thought to be one of the most promising targets for the treatment of drug addiction. GABABR positive allosteric modulators (PAMs) have shown promise as potential anti-addictive therapies, as they lack the sedative and muscle relaxant properties of full GABAB receptor agonists such as baclofen. OBJECTIVES: The present study was aimed at developing novel, selective, and potent GABABR PAMs with efficacy on abuse-related effects of nicotine...
May 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28357120/gabab-receptor-allosteric-modulators-exhibit-pathway-dependent-and-species-selective-activity
#18
Emmanuel Sturchler, Xia Li, Maria de Lourdes Ladino, Kasia Kaczanowska, Michael Cameron, Patrick R Griffin, M G Finn, Athina Markou, Patricia McDonald
Positive modulation of the GABAB receptor (GABABR) represents a potentially useful therapeutic approach for the treatment of nicotine addiction. The positive allosteric modulators (PAMs) of GABABR GS39783 and BHF177 enhance GABA-stimulated [(35)S]GTP γS-binding, and have shown efficacy in a rodent nicotine self-administration procedure reflecting aspects of nicotine dependence. Interestingly, the structural related analog, NVP998, had no effect on nicotine self-administration in rats despite demonstrating similar pharmacokinetic properties...
April 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28323246/the-role-of-spinal-gabab-receptors-in-cancer-induced-bone-pain-in-rats
#19
Ya-Qun Zhou, Shu-Ping Chen, Dai-Qiang Liu, Anne Manyande, Wen Zhang, Shao-Bing Yang, Bing-Rui Xiong, Qiao-Chu Fu, Zhen-Peng Song, Heike Rittner, Da-Wei Ye, Yu-Ke Tian
Cancer-induced bone pain (CIBP) remains a major challenge in advanced cancer patients because of our lack of understanding of its mechanisms. Previous studies have shown the vital role of γ-aminobutyric acid B receptors (GABABRs) in regulating nociception and various neuropathic pain models have shown diminished activity of GABABRs. However, the role of spinal GABABRs in CIBP remains largely unknown. In this study, we investigated the specific cellular mechanisms of GABABRs in the development and maintenance of CIBP in rats...
March 18, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28299422/homeostatic-regulation-through-gaba-and-acetylcholine-muscarinic-receptors-of-motor-trigeminal-neurons-following-sleep-deprivation
#20
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
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