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https://www.readbyqxmd.com/read/28213518/deficits-in-the-activity-of-presynaptic-%C3%AE-aminobutyric-acid-type-b-receptors-contribute-to-altered-neuronal-excitability-in-fragile-x-syndrome
#1
Ji-Yong Kang, Jayashree Chadchankar, Thuy N Vien, Michelle I Mighdoll, Thomas M Hyde, Robert J Mather, Tarek Z Deeb, Menelas N Pangalos, Nicholas J Brandon, John Dunlop, Stephen J Moss
The behavioral and anatomical deficits seen in Fragile X syndrome (FXS) are widely believed to result from imbalances in the relative strengths of excitatory and inhibitory neurotransmission. While modified neuronal excitability is thought to be of significance, the contribution that alterations in GABAergic inhibition play in the pathophysiology of FXS are ill-defined. Slow sustained neuronal inhibition is mediated by γ-aminobutyric acid type B (GABAB) receptors, which are heterodimeric G-protein coupled receptors constructed from R1a and R2 or R1b and R2 subunits...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28212175/advances-in-epilepsy-gene-discovery-and-implications-for-epilepsy-diagnosis-and-treatment
#2
Joseph D Symonds, Sameer M Zuberi, Michael R Johnson
PURPOSE OF REVIEW: Epilepsy genetics is shifting from the academic pursuit of gene discovery to a clinical discipline based on molecular diagnosis and stratified medicine. We consider the latest developments in epilepsy genetics and review how gene discovery in epilepsy is influencing the clinical classification of epilepsy and informing new therapeutic approaches and drug discovery. RECENT FINDINGS: Recent studies highlighting the importance of mutation in GABA receptors, NMDA receptors, potassium channels, G-protein coupled receptors, mammalian target of rapamycin pathway and chromatin remodeling are discussed...
February 15, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28210205/the-atp-gated-p2x7-receptor-as-a-target-for-the-treatment-of-drug-resistant-epilepsy
#3
REVIEW
Edward Beamer, Wolfgang Fischer, Tobias Engel
Despite the progress made in the development of new antiepileptic drugs (AEDs), the biggest challenges that epilepsy presents to drug development have remained unchanged for the last 80 years: finding a treatment with potential for modifying disease progression and reducing the percentage of patients resistant to all pharmacological interventions. The mechanism of action of the majority of AEDs is based on blocking Na(+) and/or Ca(2+) channels, promotion of GABA or inhibition of glutamate signaling. In order for further progress to be made, however, a fuller picture of epilepsy will need to be considered, including changes to blood-brain barrier permeability, synaptic plasticity, network reorganization, and gliosis...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28199198/the-immunological-function-of-gabaergic-system
#4
Chenlu Wu, Xiaobin Qin, Huihui Du, Nengzhang Li, Wenkai Ren, Yuanyi Peng
As a well-known inhibitory neurotransmitter in the central nervous system, gamma-aminobutyric acid also has critical roles in immune system. Immune cells (e.g., lymphocytes, macrophages) express the components of GABAergic system, including GABA receptors, GABA transporters, and GABA metabolic enzymes. The functions of immune cells are highly impacted on GABA signaling. GABAergic components negatively regulate the immune responses, particularly the T cell-mediated immunity, via their effects on production of pro-inflammatory cytokines and activation of signal pathways, like mitogen-activated protein kinase and nuclear factor-kappaB pathways...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28198153/chronic-stress-in-lizards-studies-on-the-behavior-and-benzodiazepine-receptors-in-liolaemus-koslowskyi-and-cnemidophorus-tergolaevigatus
#5
Alejandra Soloaga, Mariana Pueta, Félix Benjamín Cruz, Jackelyn Melissa Kembro, Raul Hector Marin
Behavioral and physiological adaptive responses of animals facing chronic exposure to a single stressor may allow them to overcome its negative effects for future exposures to similar stressful situations. At chemical level, the GABAA /benzodiazepine complex is considered one of the main receptor systems involved in the modulation of stress-induced responses. Here, we describe the behavioral responses of two different lizard species, Liolaemus koslowskyi and Cnemidophorus tergolaevigatus exposed to three potential chronic stressful treatments: (a) high temperature, (b) forced swimming, and (c) simulated predator...
December 2016: Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology
https://www.readbyqxmd.com/read/28197552/altered-channel-conductance-states-and-gating-of-gabaa-receptors-by-a-pore-mutation-linked-to-dravet-syndrome
#6
Ciria C Hernandez, Weijing Kong, Ningning Hu, Yujia Zhang, Wangzhen Shen, Laurel Jackson, Xiaoyan Liu, Yuwu Jiang, Robert L Macdonald
We identified a de novo missense mutation, P302L, in the γ-aminobutyric acid type A (GABAA) receptor γ2 subunit gene GABRG2 in a patient with Dravet syndrome using targeted next-generation sequencing. The mutation was in the cytoplasmic portion of the transmembrane segment M2 of the γ2 subunit that faces the pore lumen. GABAA receptor α1 and β3 subunits were coexpressed with wild-type (wt) γ2L or mutant γ2L(P302L) subunits in HEK 293T cells and cultured mouse cortical neurons. We measured currents using whole-cell and single-channel patch clamp techniques, surface and total expression levels using surface biotinylation and Western blotting, and potential structural perturbations in mutant GABAA receptors using structural modeling...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28197549/activation-dependent-rapid-postsynaptic-clustering-of-glycine-receptors-in-mature-spinal-cord-neurons
#7
Yoshihisa Nakahata, Kei Eto, Hideji Murakoshi, Miho Watanabe, Toshihiko Kuriu, Hiromi Hirata, Andrew J Moorhouse, Hitoshi Ishibashi, Junichi Nabekura
Inhibitory synapses are established during development but continue to be generated and modulated in strength in the mature nervous system. In the spinal cord and brainstem, presynaptically released inhibitory neurotransmitter dominantly switches from GABA to glycine during normal development in vivo. While presynaptic mechanisms of the shift of inhibitory neurotransmission are well investigated, the contribution of postsynaptic neurotransmitter receptors to this shift is not fully elucidated. Synaptic clustering of glycine receptors (GlyRs) is regulated by activation-dependent depolarization in early development...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28196966/effect-of-selective-5-ht6r-agonist-on-expression-of-5-ht-receptor-and-neurotransmitter-in-vascular-dementia-rats
#8
Haining Yu, Tao Chen, Li Zhou, Jiyou Tang
BACKGROUND 5-HT6 receptor (5-HT6R) has pluripotent roles regulating secretion of neurotransmitters. However, whether 5-HT6R is involved in the development of vascular dementia (VD) remains unclear. To evaluate the role and mechanism of 5-HT6R in VD, this study established a rat VD model to evaluate the effect of selective 5-HT6R agonist on the expression of 5-HT6R mRNA and neurotransmitter. MATERIAL AND METHODS Eighty healthy male SD rats (7 weeks old) were randomly assigned to sham, model, 5-HT6R agonist, and placebo groups (N=20 each)...
February 15, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28196855/inactivation-of-girk-channels-weakens-the-pre-and-postsynaptic-inhibitory-activity-in-dorsal-raphe-neurons
#9
Nerea Llamosas, Luisa Ugedo, Maria Torrecilla
The serotonergic tone of the dorsal raphe (DR) is regulated by 5-HT1A receptors, which negatively control serotonergic activity via the activation of G protein-coupled inwardly rectifying K(+) (GIRK) channels. In addition, DR activity is modulated by local GABAergic transmission, which is believed to play a key role in the development of mood-related disorders. Here, we sought to characterize the role of GIRK2 subunit-containing channels on the basal electrophysiological properties of DR neurons and to investigate whether the presynaptic and postsynaptic activities of 5-HT1A, GABAB, and GABAA receptors are affected by Girk2 gene deletion...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28194935/a-potential-pet-radiotracer-for-the-5-ht2c-receptor-synthesis-and-in-vivo-evaluation-of-4-3-18-f-fluorophenethoxy-pyrimidine
#10
Juhyeon Kim, Byung Seok Moon, Byung Chul Lee, Ho-Young Lee, Hak Joong Kim, Hyunah Choo, Ae Nim Pae, Yong Seo Cho, Sun-Joon Min
The serotonin 2C receptor subtype (5-HT2C) is an excitatory 5-HT receptor widely distributed throughout the central nerve system. As the 5-HT2C receptor displays multiple actions on various neurotransmitter systems including glutamate, dopamine, epinephrine and -aminobutyric acid (GABA), abnormalities of the 5-HT2C receptor are associated with psychiatric diseases such as depression, schizophrenia, drug abuse, and anxiety. Up to date, three kinds of 5-HT2C PET radiotracers such as [11C]N-methylated arylazepine (1), [11C]WAY-163909 (2), [18F]fluorophenylcyclopropane (3) have been developed, but they may not be suitable for in vivo 5-HT2C imaging study due to their modest specific binding...
February 14, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28194132/molecular-imaging-markers-to-track-huntington-s-disease-pathology
#11
REVIEW
Heather Wilson, Rosa De Micco, Flavia Niccolini, Marios Politis
Huntington's disease (HD) is a progressive, monogenic dominant neurodegenerative disorder caused by repeat expansion mutation in the huntingtin gene. The accumulation of mutant huntingtin protein, forming intranuclear inclusions, subsequently leads to degeneration of medium spiny neurons in the striatum and cortical areas. Genetic testing can identify HD gene carriers before individuals develop overt cognitive, psychiatric, and chorea symptoms. Thus, HD gene carriers can be studied in premanifest stages to understand and track the evolution of HD pathology...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28192622/the-safety-and-efficacy-of-baclofen-to-reduce-alcohol-use-in-veterans-with-chronic-hepatitis-c-a-randomized-clinical-trial
#12
Peter Hauser, Bret Fuller, Samuel B Ho, Paul Thuras, Shira Kern, Eric Dieperink
BACKGROUND AND AIMS: Alcohol use disorders (AUDs) are common among people with chronic hepatitis C (HCV) and accelerate the development of fibrosis and cirrhosis caused by HCV. Baclofen, a gamma-aminobutyric acid (GABA) beta-receptor agonist, differs from medications for AUDs currently approved by the United States (US) Federal Drug Administration (FDA) as it is metabolized primarily through the kidneys. The primary outcome of this study was to compare baclofen with a placebo in the percentage of days abstinent from alcohol...
February 13, 2017: Addiction
https://www.readbyqxmd.com/read/28190395/gabaergic-system-in-action-connection-to-gastrointestinal-stress-related-disorders
#13
Maja Jazvinšćak Jembrek, Michelangelo Auteri, Rosa Serio, Josipa Vlainić
BACKGROUND: Currently, treatment of stress-related gastrointestinal disorders, such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), is mainly symptomatic since there is no drug on the market that solves effectively diverse disease symptoms and comorbid states. Thus, recently GABA receptors have been identified within gastrointestinal system and it has been recognized that among various GABAergic drugs some of them influence gastrointestinal stress-related diseases...
February 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28188663/histamine-facilitates-gabaergic-transmission-in-the-rat-entorhinal-cortex-roles-of-h1-and-h2-receptors-na-permeable-cation-channels-and-inward-rectifier-k-channels
#14
Nicholas I Cilz, Saobo Lei
In the brain, histamine (HA) serves as a neuromodulator and a neurotransmitter released from the tuberomammillary nucleus (TMN). HA is involved in wakefulness, thermoregulation, energy homeostasis, nociception and learning and memory. The medial entorhinal cortex (MEC) receives inputs from the TMN and expresses HA receptors (H1 , H2 , and H3 ). We investigated the effects of HA on GABAergic transmission in the MEC and found that HA significantly increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) with an EC50 of 1...
February 11, 2017: Hippocampus
https://www.readbyqxmd.com/read/28188217/hebbian-spike-timing-dependent-plasticity-at-the-cerebellar-input-stage
#15
M Sgritta, F Locatelli, T Soda, F Prestori, E D'Angelo
Spike-timing dependent plasticity (STDP) is a form of long-term synaptic plasticity exploiting the time relationship between postsynaptic action potentials (AP) and EPSPs. Surprisingly enough, very little was known about STDP in the cerebellum, although it is thought to play a critical role for learning appropriate timing of actions. We speculated that low-frequency oscillations observed in the granular layer may provide a reference for repetitive EPSP/AP phase coupling. Here we show that EPSP-spike pairing at 6Hz can optimally induce STDP at the mossy fiber - granule cell synapse in rats...
February 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28188055/the-emergency-medicine-management-of-severe-alcohol-withdrawal
#16
Drew Long, Brit Long, Alex Koyfman
INTRODUCTION: Alcohol use is widespread, and withdrawal symptoms are common after decreased alcohol intake. Severe alcohol withdrawal may manifest with delirium tremens, and new therapies may assist in management of this life-threatening condition. OBJECTIVE: To provide an evidence-based review of the emergency medicine management of alcohol withdrawal and delirium tremens. DISCUSSION: The underlying pathophysiology of alcohol withdrawal syndrome (AWS) is central nervous system hyperexcitation...
February 4, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28187828/molecular-characterization-and-expression-pattern-of-three-gaba-receptor-like-subunits-in-the-small-brown-planthopper-laodelphax-striatellus-hemiptera-delphacidae
#17
Qi Wei, Shun-Fan Wu, Cong-Fen Gao
Ionotropic γ-aminobutyric acid (GABA)-gated chloride channel receptors mediate rapid inhibitory neurotransmission in vertebrates and invertebrates. GABA receptors are well known to be the molecular targets of synthetic insecticides or parasiticides. Three GABA receptor-like subunits, LsLCCH3, LsGRD and LS8916, of the small brown planthopper, Laodelphax striatellus (Fallén), a major insect pest of crop systems in East Asia, had been identified and characterized in this study. All three genes were cloned using the reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE)...
March 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/28186121/astrocyte-deletion-of-bmal1-alters-daily-locomotor-activity-and-cognitive-functions-via-gaba-signalling
#18
Olga Barca-Mayo, Meritxell Pons-Espinal, Philipp Follert, Andrea Armirotti, Luca Berdondini, Davide De Pietri Tonelli
Circadian rhythms are controlled by a network of clock neurons in the central pacemaker, the suprachiasmatic nucleus (SCN). Core clock genes, such as Bmal1, are expressed in SCN neurons and in other brain cells, such as astrocytes. However, the role of astrocytic clock genes in controlling rhythmic behaviour is unknown. Here we show that ablation of Bmal1 in GLAST-positive astrocytes alters circadian locomotor behaviour and cognition in mice. Specifically, deletion of astrocytic Bmal1 has an impact on the neuronal clock through GABA signalling...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28178754/neuroprotective-effect-of-nebivolol-against-cisplatin-associated-depressive-like-behavior-in-rats
#19
Noha F Abdelkader, Muhammed A Saad, Rania M Abdelsalam
One-third of cancer patients undergoing chemotherapy treatment often display symptoms of depression leading to poor adherence and decreased quality of life. Thus, the current study aimed to investigate the possible protective effect of nebivolol against cisplatin associated depressive symptoms in adult male rats. Nebivolol is a highly cardioselective β-adrenergic receptor blocker that possesses endothelium-dependent vasodilator properties and antioxidant capacities. Animals were allocated into four groups...
February 8, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28176641/gaba-a-receptor-subtypes-implications-for-the-treatment-of-pain
#20
Bradford D Fischer
Chronic severe pain is treated most successfully with opioid analgesics, although the clinical use of these drugs is constrained by unwanted side effects, including the potential for abuse. GABAergic neurons are located in spinal nociceptive circuits suggesting that drugs with affinity at these receptors, including benzodiazepine-like drugs, may provide an alternative to opioids for the treatment of pain. However, systemically administered conventional benzodiazepines fail to produce antihyperalgesic effects, likely due to their concurrent sedative properties...
February 7, 2017: CNS & Neurological Disorders Drug Targets
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