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https://www.readbyqxmd.com/read/29504979/autoimmune-encephalitis-positive-for-both-anti-%C3%AE-aminobutyric-acid-b-receptor-and-anticollapsin-response-mediator-protein-5-antibodies-a-case-report
#1
Junyang Xia, Xiaoming Yin, Mingqin Zhu, Jie Cao, Xiaonan Song
RATIONALE: Autoimmune encephalitis (AE) is a heterogeneous group of recently identified disorders. Despite severe and even prolonged neurologic deficits, dramatic improvements may occur with proper immunotherapy in some patients with AE. Antineuronal antibodies have been discovered in patients' serum and cerebrospinal fluid (CSF). However, AE with multiple antineuronal antibodies is rare. To date, there are no published reports of AE with both anti-γ-aminobutyric acid B receptor (GABABR) and anticollapsin response-mediator protein 5 (CV2) antibodies...
January 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29407219/gaba-a-receptor-positive-and-negative-allosteric-modulators
#2
REVIEW
Richard W Olsen
gamma-Aminobutyric acid (GABA)-mediated inhibitory neurotransmission and the gene products involved were discovered during the mid-twentieth century. Historically, myriad existing nervous system drugs act as positive and negative allosteric modulators of these proteins, making GABA a major component of modern neuropharmacology, and suggesting that many potential drugs will be found that share these targets. Although some of these drugs act on proteins involved in synthesis, degradation, and membrane transport of GABA, the GABA receptors Type A (GABAA R) and Type B (GABABR) are the targets of the great majority of GABAergic drugs...
January 30, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29332416/-autoimmune-encephalitis-possibilities-in-the-laboratory-investigation
#3
Katalin Böröcz, Zsófia Hayden, Viktória Mészáros, Zsuzsanna Csizmadia, Kornélia Farkas, Zoltán Kellermayer, Péter Balogh, Ferenc Nagy, Tímea Berki
INTRODUCTION: The role of autoimmune responses against central nervous system (CNS) antigens in encephalitis presenting with non-classified neurologic or psychiatric symptoms has been appreciated in the past decade. Paraneoplastic limbic encephalitis has a poor prognosis and is most commonly associated with lung, ovarium, and testicular neoplasms, leading to immune reactions against intracellular antigens (anti-Hu/ANNA1, anti-Ri/ANNA2, anti-CV2/CRMP5 and anti-Ma2/Ta). In contrast, the recently described autoimmune encephalitis subtypes present with a broad spectrum of symptoms, respond to autoimmune therapies well and usually associate with autoantibodies against neuronal cell surface receptors (NMDAR, GABAB R, AMPAR) or synaptic proteins (LGI1, CASPR2)...
January 2018: Orvosi Hetilap
https://www.readbyqxmd.com/read/29298431/postsynaptic-gaba-b-rs-inhibit-l-type-calcium-channels-and-abolish-long-term-potentiation-in-hippocampal-somatostatin-interneurons
#4
Sam A Booker, Desiree Loreth, Annabelle L Gee, Masahiko Watanabe, Peter C Kind, David J A Wyllie, Ákos Kulik, Imre Vida
Inhibition provided by local GABAergic interneurons (INs) activates ionotropic GABAA and metabotropic GABAB receptors (GABAB Rs). Despite GABAB Rs representing a major source of inhibition, little is known of their function in distinct IN subtypes. Here, we show that, while the archetypal dendritic-inhibitory somatostatin-expressing INs (SOM-INs) possess high levels of GABAB R on their somato-dendritic surface, they fail to produce significant postsynaptic inhibitory currents. Instead, GABAB Rs selectively inhibit dendritic CaV 1...
January 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/29209452/protective-roles-of-hepatic-gaba-signaling-in-liver-injury
#5
Shuanglian Wang, Lu Zhang, Chuanyong Liu, Wei-Yang Lu
In addition to functioning as a neurotransmitter, γ-aminobutyric acid (GABA) generates signals, via its type A or type B receptors (GABAA Rs or GABAB Rs), in various types of cells. Studies, including ours, show that GABAA R-mediated auto- and paracrine GABAergic signaling occurs in rodent hepatocytes and cholangiocytes, protecting the liver against toxic injuries. This short article briefly introduces the GABA signaling system in rodent livers and discusses potential mechanisms by which the hepatic GABA signaling protects the liver function...
2017: International Journal of Physiology, Pathophysiology and Pharmacology
https://www.readbyqxmd.com/read/29166136/the-gamma-aminobutyric-acid-b-receptor-gabab-encephalitis-clinical-manifestations-and-response-to-immunotherapy
#6
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 analyze 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: Of the 11 patients, seven were males, and a mean age at presentation of 63 years (range: 47-79 years)...
December 6, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/29163811/impaired-gaba-b-mediated-presynaptic-inhibition-increases-excitatory-strength-and-alters-short-term-plasticity-in-synapsin-knockout-mice
#7
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 (GABAB Rs)...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133952/engaging-homeostatic-plasticity-to-treat-depression
#8
E R Workman, F Niere, K F Raab-Graham
Major depressive disorder (MDD) is a complex and heterogeneous mood disorder, making it difficult to develop a generalized, pharmacological therapy that is effective for all who suffer from MDD. Through the fortuitous discovery of N-methyl-D-aspartate receptor (NMDAR) antagonists as effective antidepressants, we have gained key insights into how antidepressant effects can be produced at the circuit and molecular levels. NMDAR antagonists act as rapid-acting antidepressants such that relief from depressive symptoms occurs within hours of a single injection...
January 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29075658/improving-the-antibody-based-evaluation-of-autoimmune-encephalitis
#9
Lindsey McCracken, Junxian Zhang, Maxwell Greene, Anne Crivaro, Joyce Gonzalez, Malek Kamoun, Eric Lancaster
OBJECTIVE: We tested whether antibody screening samples of patients with suspected autoimmune encephalitis with additional research assays would improve the detection of autoimmune encephalitis compared with standard clinical testing alone. METHODS: We examined 731 samples (333 CSF, 182 sera, and 108 pairs) from a cohort of 623 patients who were tested for CNS autoantibodies by the University of Pennsylvania clinical laboratory over a 24-month period with cell-based assays (CBAs) on commercially obtained slides of fixed cells for antibodies to NMDA receptor (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), γ-aminobutyric acid-B receptor (GABAB R), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (Caspr2), and glutamic acid decarboxylase (GAD65)...
November 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/29042314/differential-distribution-and-function-of-gababrs-in-somato-dendritic-and-axonal-compartments-of-principal-cells-and-interneurons-in-cortical-circuits
#10
REVIEW
Ákos Kulik, Sam A Booker, Imre Vida
GABABRs are highly expressed in cortical circuits, controlling neuronal excitability and synaptic transmission in both principal cells and inhibitory interneurons. Light and electron microscopic studies confirmed the wide distribution of receptors and revealed cell type-specific quantitative differences in their cellular and subcellular distributions. At the subcellular level, GABABRs are abundant at the peri- and extrasynaptic membrane of somato-dendritic compartments and to lower levels in the axon terminals of both cortical excitatory principal cells and inhibitory interneurons...
October 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29038006/role-of-ca1-gaba-a-and-gaba-b-receptors-on-learning-deficit-induced-by-d-ap5-in-passive-avoidance-step-through-task
#11
Mohaddeseh Ebrahimi-Ghiri, Masoumeh Rostampour, Mehdi Jamshidi-Mehr, Mohammad Nasehi, Mohammad-Reza Zarrindast
To investigate the interaction between hippocampal γ-aminobutyric acid GABAA receptor (GABAA R) or GABAB receptor (GABAB R) and N-methyl-D-aspartate receptor (NMDAR) in the acquisition of passive avoidance memory in rats, we used GABAA or GABAB agents, D-AP5 (as a NMDAR antagonist), and a combination of the mentioned drugs in a step-through task. All agents were microinjected into the intra-CA1 regions at a volume of 1 µl/rat, prior to training. GABAA R agonist muscimol (0.2 µg/rat), selective GABAB R agonist baclofen (0...
January 1, 2018: Brain Research
https://www.readbyqxmd.com/read/29028808/functional-characterization-of-gabaa-receptor-mediated-modulation-of-cortical-neuron-network-activity-in-microelectrode-array-recordings
#12
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
#13
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 epilepsy surgery due to mesial TLE-HS were included. The sera of patients are tested for neuronal antibodies to N-methyl-D-aspartate receptors (NMDAR), leucine-rich, glioma inactivated 1 (LGI1), contactin-associated protein 2 (CASPR2), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), gamma-aminobutyric acid B receptor (GABABR) and glutamic acid decarboxylase (GAD)...
November 16, 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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