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https://www.readbyqxmd.com/read/28647593/features-of-emotional-and-social-behavioral-phenotypes-of-calsyntenin2-knockout-mice
#1
S V Ranneva, K S Pavlov, A V Gromova, T G Amstislavskaya, T V Lipina
Calsyntenin-2 (Clstn2) is the synaptic protein that belongs to the super family of cadherins, playing an important role in learning and memory. We recently reported that Clstn2 knockout mice (Clstn2-KO) have a deficit of GABAergic interneurons coupled with hyperactivity and deficient spatial memory. Given, that impaired functioning of GABA receptors is linked to several psychopathologies, including anxiety and autism, we sought to further characterize Clstn2-KO mice with respect to emotional and social behavior...
June 21, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28646451/regulation-of-sustained-attention-false-alarm-responding-and-implementation-of-conditional-rules-by-prefrontal-gabaa-transmission-comparison-with-nmda-transmission
#2
Meagan L Auger, Juliet Meccia, Stan B Floresco
RATIONALE: Both prefrontal cortex (PFC) GABAA and NMDA transmission regulate attentional processes, yet how they may differentially regulate signal detection or other aspects of attention is unclear. OBJECTIVES: We examined PFC GABAA and NMDA receptor regulation of attention using a sustained attention task (SAT) permitting identification of distinct forms of impairments. As this task requires implementation of conditional rules, we also investigated how reducing PFC GABA transmission affected performance of visual and auditory conditional discriminations...
June 24, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28642681/%C3%AE-1-containing-gaba-a-receptors-cluster-at-synapses-where-they-mediate-slower-synaptic-currents-than-%C3%AE-2-containing-gaba-a-receptors
#3
Christine L Dixon, Pankaj Sah, Angelo Keramidas, Joseph W Lynch, Nela Durisic
GABA-A receptors (GABAARs) are pentameric ligand-gated ion channels that are assembled mainly from α (α1-6), β (β1-3) and γ (γ1-3) subunits. Although GABAARs containing γ2L subunits mediate most of the inhibitory neurotransmission in the brain, significant expression of γ1 subunits is seen in the amygdala, pallidum and substantia nigra. However, the location and function of γ1-containing GABAARs in these regions remains unclear. In "artificial" synapses, where the subunit composition of postsynaptic receptors is specifically controlled, γ1 incorporation slows the synaptic current decay rate without affecting channel deactivation, suggesting that γ1-containing receptors are not clustered and therefore activated by diffuse neurotransmitter...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28642284/excitation-of-gabaergic-neurons-in-the-bed-nucleus-of-the-stria-terminalis-triggers-immediate-transition-from-non-rapid-eye-movement-sleep-to-wakefulness-in-mice
#4
Shota Kodani, Shingo Soya, Takeshi Sakurai
Emotionally salient situations usually trigger arousal along with autonomic and neuroendocrine reactions. To examine whether the extended amygdala plays a role in sleep/wakefulness regulation, we examined the effects of optogenetic and pharmacogenetic excitation of GABAergic neurons in the bed nucleus of the stria terminalis (GABA(BNST) neurons). Acute optogenetic excitation of these cells during non-rapid eye movement (NREM) sleep resulted in immediate state transition to wakefulness, while stimulation during rapid eye movement (REM) sleep showed no effect on sleep/wakefulness states in male mice...
June 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28642282/kappa-opioid-receptors-mediate-heterosynaptic-suppression-of-hippocampal-inputs-in-the-rat-ventral-striatum
#5
Julie Brooks, Patricio O'Donnell
Kappa opioid receptors (KOR) 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 prefrontal cortex (PFC) and limbic regions, such as the hippocampus (HP)...
June 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28638920/-a-study-on-toxic-effects-of-sodium-salicylate-on-rat-cochlear-spiral-ganglion-neurons-dopamine-receptors-mediate-expressions-of-nmda-and-gabaa-receptors
#6
Ting-Jia Wei, Hui-Ying Chen, Xi Huang, Jing-Jin Weng, Jiang-Yuan Qin, Ji-Ping Su
The aim of the present study was to observe whether dopamine receptor (DR) was involved in the effects of sodium salicylate (SS) on the expressions of N-methyl-D-aspartic acid (NMDA) and γ-aminobutyric acid (GABA) receptors in rat cochlear spiral ganglion neurons (SGNs). Forty-eight hours after primary culture of rat SGNs, immunofluorescence technique was applied to detect expressions of DR1 and DR2, the two subtypes of dopamine receptors. Western blot was performed to assess NMDA receptor NR1 subunit and GABAA receptor subunit α2 (GABRα2) protein expressions in the SGNs after the treatments of SS alone or in combination with DR antagonists...
June 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28635673/toxicity-of-naphthalene-and-benzene-on-tribollium-castaneum-herbst
#7
Nerlis Pajaro-Castro, Karina Caballero-Gallardo, Jesus Olivero-Verbel
Naphthalene and benzene are widely-used volatile organic compounds. The aim of this research was to examine the toxicological effects of naphthalene and benzene against Tribolium castaneum as an animal model. Adult insects were exposed to these aromatic compounds to assess mortality after 4-48 h of exposure. The lethal concentration 50 (LC50) for naphthalene, naphthalin, and benzene were 63.6 µL/L, 20.0 µL/L, and 115.9 µL/L in air, respectively. Real-time polymerase chain reaction (PCR) analysis revealed expression changes in genes related to oxidative stress and metabolism [Glutathione S-Transferase (Gst), and Cytochrome P450 6BQ8 (Cyp6bq8)]; reproduction and metamorphosis [Hormone receptor in 39-like protein (Hr39), Ecdysone receptor: (Ecr), and Chitin synthase 2 (Chs2)]; and neurotransmission [Histamine-gated chloride channel 2 (Hiscl2)] in insects exposed for 4 h to 70...
June 21, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28632130/the-laminar-organization-of-the-drosophila-ellipsoid-body-is-semaphorin-dependent-and-prevents-the-formation-of-ectopic-synaptic-connections
#8
Xiaojun Xie, Masashi Tabuchi, Matthew P Brown, Sarah P Mitchell, Mark N Wu, Alex L Kolodkin
The ellipsoid body (EB) in the Drosophila brain is a central complex (CX) substructure that harbors circumferentially laminated ring (R) neuron axons and mediates multifaceted sensory integration and motor coordination functions. However, what regulates R axon lamination and how lamination affects R neuron function remain unknown. We show here that the EB is sequentially innervated by small-field and large-field neurons, and that early-developing EB neurons play an important regulatory role in EB laminae formation...
June 20, 2017: ELife
https://www.readbyqxmd.com/read/28631579/opening-of-katp-channel-regulates-tonic-currents-from-pyramidal-neurons-in-rat-brain
#9
Zhongxia Li, Jiangping Wang, Huimin Yu, Kewen Jiang
BACKGROUND: ATP-sensitive K+ (KATP) channels couple metabolic state to cellular excitability. Activation of neuronal and astrocytic mitochondrial KATP (mitoKATP) channels regulates a variety of neuronal functions. However, less is known about the impact of mitoKATP on tonic γ-aminobutyric acid (GABA) inhibition. Tonic GABA inhibition is mediated by the binding of ambient GABA on extrasynaptic GABA A-type receptors (GABAARs) and is involved in regulating neuronal excitability. METHODS: We determined the impact of activation of KATP channels with diazoxide (DIZ) on tonic inhibition and recorded tonic current from rat cortical layer 5 pyramidal cells by patch-clamp recordings...
June 20, 2017: Canadian Journal of Neurological Sciences. le Journal Canadien des Sciences Neurologiques
https://www.readbyqxmd.com/read/28629847/evidence-for-m2-muscarinic-receptor-modulation-of-axon-terminals-and-dendrites-in-the-rodent-basolateral-amygdala-an-ultrastructural-and-electrophysiological-analysis
#10
Ana Fajardo-Serrano, Lei Liu, David D Mott, Alexander J McDonald
The basolateral amygdala receives a very dense cholinergic innervation from the basal forebrain that is important for memory consolidation. Although behavioral studies have shown that both M1 and M2 muscarinic receptors are critical for these mnemonic functions, there have been very few neuroanatomical and electrophysiological investigations of the localization and function of different types of muscarinic receptors in the amygdala. In the present study we investigated the subcellular localization of M2 muscarinic receptors (M2Rs) in the anterior basolateral nucleus (BLa) of the mouse, including the localization of M2Rs in parvalbumin (PV) immunoreactive interneurons, using double-labeling immunoelectron microscopy...
June 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28623169/mutation-of-the-inhibitory-ethanol-site-in-gabaa-%C3%AF-1-receptors-promotes-tolerance-to-ethanol-induced-motor-incoordination
#11
Yuri A Blednov, Cecilia M Borghese, Carlos I Ruiz, Madeline A Cullins, Adriana Da Costa, Elizabeth A Osterndorff-Kahanek, Gregg E Homanics, R Adron Harris
Genes encoding the ρ1/2 subunits of GABAA receptors have been associated with alcohol (ethanol) dependence in humans, and ρ1 was also shown to regulate some of the behavioral effects of ethanol in animal models. Ethanol inhibits GABA-mediated responses in wild-type (WT) ρ1, but not ρ1(T6'Y) mutant receptors expressed in Xenopus laevis oocytes, indicating the presence of an inhibitory site for ethanol in the second transmembrane helix. In this study, we found that ρ1(T6'Y) receptors expressed in oocytes display overall normal responses to GABA, the endogenous GABA modulator (zinc), and partial agonists (β-alanine and taurine)...
June 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28621878/isolation-and-chemical-characterization-of-agelaiatoxin8-avtx8-from-agelaia-vicina-wasp-venom-and-its-biological-effects-on-gaba-neurotransmission
#12
Andrea B Pizzo, Renê O Beleboni, Ruither O Gomes Carolino, Luciana de Oliveira, Antonio Miranda, Joaquim Coutinho-Netto, Andréia C K Fontana, Wagner Ferreira Dos Santos
Arthropod venoms are sources of molecules that may be useful tools to investigate molecular mechanisms of putative new medicines and laboratory drugs. Here we show the effects of the compound agelaiatoxin-8 (AVTx8), isolated from Agelaia vicina venom, on γ-aminobutyric acid (GABA) neurotransmission in rat brain synaptosomes. Analysis reveals that AvTx8 is composed by 14 amino acid residues with a molecular weight (MW) of 1567 Da. AvTx8 increased GABA release and inhibited GABA uptake in synaptosomes from rat cerebral cortex...
June 16, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28611364/association-of-polymorphisms-in-pharmacogenetic-candidate-genes-with-propofol-susceptibility
#13
Qi Zhong, Xiangdong Chen, Yan Zhao, Ru Liu, Shanglong Yao
Significant individual susceptibility to intravenous anesthetic propofol exists. The etiology of individual variability in the response to propofol may be influenced by genetic polymorphisms in metabolic and functional pathways. With current pharmacogenetics and modern molecular biology technologies, it is possible to study the influence of genetic polymorphisms on susceptibility to propofol. When inducing general anesthesia with intravenous propofol, high individual susceptibility to propofol was found. Using Sequenom MassARRAY single-nucleotide polymorphism (SNP) genotyping, we identified a mutation (rs6313) in the 5HT2A gene that was correlated to individual susceptibility to propofol effect-site concentration (Cep) and onset time of propofol induction...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28610974/positive-modulation-of-%C3%AE-5-gabaa-receptors-in-preadolescence-prevents-reduced-locomotor-response-to-amphetamine-in-adult-female-but-not-male-rats-prenatally-exposed-to-lipopolysaccharide
#14
Bojan Batinić, Anja Santrač, Ivan Jančić, Guanguan Li, Aleksandra Vidojević, Bojan Marković, James M Cook, Miroslav M Savić
We previously demonstrated that lipopolysaccharide (LPS) administered intraperitoneally (i.p.) to pregnant Wistar rat dams, at embryonic days 15 and 16 (E15/16), induced a decrease of baseline locomotor activity and diminished reactivity to amphetamine in adult female offspring. In the present study we aimed to assess the duration of LPS-induced maternal immune activation (MIA) and investigate possible changes in levels of main neurotransmitters in fetal brain during MIA. We hypothesized that the observed behavioral changes may be linked with MIA-induced disturbance of prenatal GABAergic system development, especially with α5 GABAA receptors (α5GABAARs), expression of which takes place between E14 and E17...
June 10, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28608461/epidermal-growth-factor-signals-attenuate-phenotypic-and-functional-development-of-neocortical-gaba-neurons
#15
Hisaaki Namba, Tadasato Nagano, Eiichi Jodo, Satoshi Eifuku, Masao Horie, Hirohide Takebayashi, Yuriko Iwakura, Hidekazu Sotoyama, Nobuyuki Takei, Hiroyuki Nawa
Phenotypic development of neocortical GABA neurons is highly plastic and promoted by various neurotrophic factors such as neuregulin-1. A subpopulation of GABA neurons expresses not only neuregulin receptor (ErbB4) but also epidermal growth factor (EGF) receptor (ErbB1) during development, but the neurobiological action of EGF on this cell population is less understood than that of neuregulin-1. Here we examined the effects of exogenous EGF on immature GABA neurons both in culture and in vivo and also explored physiological consequences in adults...
June 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28606041/mechanisms-of-action-resistance-and-toxicity-of-insecticides-targeting-gaba-receptors
#16
Steven Buckingham, Makoto Ihara, David B Sattelle, Kazuhiko Matsuda
Ionotropic γ-aminobutyric acid (GABA)-gated chloride channels belong to the cys-loop superfamily of ligand-gated ion channels (cys-loop LGICs) and mediate fast inhibitory synaptic transmission in the nervous system and at neuromuscular junctions of insects. Insect GABA-gated cation channels have also been described. The sequencing of insect genomes has enhanced our understanding of the subunits that make up GABA receptor gene families of many species, including a genetic model organism (Drosophila melanogaster) as well as pest, vector and beneficial (pollinator) species...
June 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28604719/essential-role-for-gabarap-autophagy-proteins-in-interferon-inducible-gtpase-mediated-host-defense
#17
Miwa Sasai, Naoya Sakaguchi, Ji Su Ma, Shuhei Nakamura, Tsuyoshi Kawabata, Hironori Bando, Youngae Lee, Tatsuya Saitoh, Shizuo Akira, Akiko Iwasaki, Daron M Standley, Tamotsu Yoshimori, Masahiro Yamamoto
Mammalian autophagy-related 8 (Atg8) homologs consist of LC3 proteins and GABARAPs, all of which are known to be involved in canonical autophagy. In contrast, the roles of Atg8 homologs in noncanonical autophagic processes are not fully understood. Here we show a unique role of GABARAPs, in particular gamma-aminobutyric acid (GABA)-A-receptor-associated protein-like 2 (Gabarapl2; also known as Gate-16), in interferon-γ (IFN-γ)-mediated antimicrobial responses. Cells that lacked GABARAPs but not LC3 proteins and mice that lacked Gate-16 alone were defective in the IFN-γ-induced clearance of vacuolar pathogens such as Toxoplasma...
June 12, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28601398/gaba-receptors-and-t-type-ca-2-channels-crosstalk-in-thalamic-networks
#18
REVIEW
Nathalie Leresche, Régis C Lambert
Although the thalamus presents a rather limited repertoire of GABAergic cell types compare to other CNS area, this structure is a privileged system to study how GABA impacts neuronal network excitability. Indeed both glutamatergic thalamocortical (TC) and GABAergic nucleus reticularis thalami (NRT) neurons present a high expression of T-type voltage-dependent Ca(2+) channels whose activation that shapes the output of the thalamus critically depends upon a preceding hyperpolarisation. Because of this strict dependence, a tight functional link between GABA mediated hyperpolarization and T-currents characterizes the thalamic network excitability...
June 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28598039/the-synthesis-and-evaluation-of-fluoro-trifluoromethyl-and-iodo-muscimols-as-gaba-agonists
#19
David O'Hagan, Mohd Abdul Fatah Abdul Manan, David Cordes, Alexandra Slawin, Vivian Liao, Han CHua, Mary Chebib, Michael Buehl
Halogenated analogues of the neurotoxic alkaloid muscimol were prepared with fluorine, iodine or trifluoromethyl at the 4 position of the isoxazole ring system. These compounds were investigated as agonists for GABAA receptors. Only the C-4 fluorine containing analogue proved to be an active compound in these assays. The fluoro analogue was less active than muscimol, however it showed differential activity between synaptic (2) and extrasynaptic () GABAA receptors, having a similar potency to the neurotransmitter GABA for the extrasynaptic () receptor...
June 9, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28596835/chronic-diazepam-administration-increases-the-expression-of-lcn2-in-the-cns
#20
Tomonori Furukawa, Shuji Shimoyama, Yasuo Miki, Yoshikazu Nikaido, Kohei Koga, Kazuhiko Nakamura, Koichi Wakabayashi, Shinya Ueno
Benzodiazepines (BZDs), which bind with high affinity to gamma-aminobutyric acid type A receptors (GABAA-Rs) and potentiate the effects of GABA, are widely prescribed for anxiety, insomnia, epileptic discharge, and as anticonvulsants. The long-term use of BZDs is limited due to adverse effects such as tolerance, dependence, withdrawal effects, and impairments in cognition and learning. Additionally, clinical reports have shown that chronic BZD treatment increases the risk of Alzheimer's disease. Unusual GABAA-R subunit expression and GABAA-R phosphorylation are induced by chronic BZD use...
February 2017: Pharmacology Research & Perspectives
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