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GABA receptor

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https://www.readbyqxmd.com/read/28932379/testing-the-excitation-inhibition-imbalance-hypothesis-in-a-mouse-model-of-the-autism-spectrum-disorder-in-vivo-neurospectroscopy-and-molecular-evidence-for-regional-phenotypes
#1
Joana Gonçalves, Inês R Violante, José Sereno, Ricardo A Leitão, Ying Cai, Antero Abrunhosa, Ana Paula Silva, Alcino J Silva, Miguel Castelo-Branco
BACKGROUND: Excitation/inhibition (E/I) imbalance remains a widely discussed hypothesis in autism spectrum disorders (ASD). The presence of such an imbalance may potentially define a therapeutic target for the treatment of cognitive disabilities related to this pathology. Consequently, the study of monogenic disorders related to autism, such as neurofibromatosis type 1 (NF1), represents a promising approach to isolate mechanisms underlying ASD-related cognitive disabilities. However, the NF1 mouse model showed increased γ-aminobutyric acid (GABA) neurotransmission, whereas the human disease showed reduced cortical GABA levels...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28929924/the-search-for-a-subtype-selective-pet-imaging-agent-for-the-gabaa-receptor-complex-evaluation-of-the-radiotracer-11-c-ado-in-nonhuman-primates
#2
Shu-Fei Lin, Frederic Bois, Daniel Holden, Nabeel Nabulsi, Richard Pracitto, Hong Gao, Michael Kapinos, Jo-Ku Teng, Anupama Shirali, Jim Ropchan, Richard E Carson, Charles S Elmore, Neil Vasdev, Yiyun Huang
The myriad physiological functions of γ-amino butyric acid (GABA) are mediated by the GABA-benzodiazepine receptor complex comprising of the GABAA, GABAB, and GABAC groups. The various GABAA subunits with region-specific distributions in the brain subserve different functional and physiological roles. For example, the sedative and anticonvulsive effects of classical benzodiazepines are attributed to the α1 subunit, and the α2 and α3 subunits mediate the anxiolytic effect. To optimize pharmacotherapies with improved efficacy and devoid of undesirable side effects for the treatment of anxiety disorders, subtype-selective imaging radiotracers are required to assess target engagement at GABA sites and determine the dose-receptor occupancy relationships...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28927958/defective-gabaergic-neurotransmission-in-the-nucleus-tractus-solitarius-in-mecp2-null-mice-a-model-of-rett-syndrome
#3
Chao-Yin Chen, Jacopo Di Lucente, Yen-Chu Lin, Cheng-Chang Lien, Michael A Rogawski, Izumi Maezawa, Lee-Way Jin
Rett syndrome (RTT) is a devastating neurodevelopmental disorder caused by loss-of-function mutations in the X-linked methyl-CpG binding protein 2 (Mecp2) gene. GABAergic dysfunction has been implicated contributing to the respiratory dysfunction, one major clinical feature of RTT. The nucleus tractus solitarius (NTS) is the first central site integrating respiratory sensory information that can change the nature of the reflex output. We hypothesized that deficiency in Mecp2 gene reduces GABAergic neurotransmission in the NTS...
September 16, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28923971/prolactin-action-in-the-medial-preoptic-area-is-necessary-for-postpartum-maternal-nursing-behavior
#4
Rosemary S E Brown, Mari Aoki, Sharon R Ladyman, Hollian R Phillipps, Amanda Wyatt, Ulrich Boehm, David R Grattan
Pregnancy hormones, such as prolactin, sensitize neural circuits controlling parental interactions to induce timely activation of maternal behaviors immediately after parturition. While the medial preoptic area (MPOA) is known to be critical for maternal behavior, the specific role of prolactin in this brain region has remained elusive. Here, we evaluated the role of prolactin action in the MPOA using complementary genetic strategies in mice. We characterized prolactin-responsive neurons within the MPOA at different hormonal stages and delineated their projections in the brain...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923348/stimulation-of-accumbal-gabaa-receptors-inhibits-delta2-but-not-delta1-opioid-receptor-mediated-dopamine-efflux-in-the-nucleus-accumbens-of-freely-moving-rats
#5
Yuri Aono, Yuri Kiguchi, Yuriko Watanabe, John L Waddington, Tadashi Saigusa
The nucleus accumbens contains delta-opioid receptors that may reduce inhibitory neurotransmission. Reduction in GABAA receptor-mediated inhibition of accumbal dopamine release due to delta-opioid receptor activation should be suppressed by stimulating accumbal GABAA receptors. As delta-opioid receptors are divided into delta2- and delta1-opioid receptors, we analysed the effects of the GABAA receptor agonist muscimol on delta2- and delta1-opioid receptor-mediated accumbal dopamine efflux in freely moving rats using in vivo microdialysis...
September 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28912643/decreased-glial-gaba-and-tonic-inhibition-in-cerebellum-of-mouse-model-for-attention-deficit-hyperactivity-disorder-adhd
#6
Yoo Sung Kim, Junsung Woo, C Justin Lee, Bo-Eun Yoon
About 5~12% of school-aged children suffer from the Attention-Deficit/Hyperactivity Disorder (ADHD). However, the core mechanism of ADHD remains unclear. G protein-coupled receptor kinase-interacting protein-1 (GIT1) has recently been reported to be associated with ADHD in human and the genetic deletion of GIT1 result in ADHD-like behaviors in mice. Mice lacking GIT1 shows a shift in neuronal excitation/inhibition (E/I) balance. However, the pricise mechanism for E/I imbalance and the role of neuron-glia interaction in GIT1 knockout (KO) mice have not been studied...
August 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28905487/endogenous-neurosteroids-influence-synaptic-gabaa-receptors-during-post-natal-development
#7
REVIEW
Delia Belelli, Adam R Brown, Scott J Mitchell, Ben G Gunn, Murray B Herd, Grant Phillips, Mohsen Seifi, Jerome D Swinny, Jeremy J Lambert
GABA plays a key role in both embryonic and neonatal brain development. For example, during early neonatal nervous system maturation, synaptic transmission, mediated by GABAA receptors (GABAA Rs), undergoes a temporally specific form of synaptic plasticity, to accommodate the changing requirements of maturing neural networks. Specifically, the duration of miniature inhibitory postsynaptic currents (mIPSCs), resulting from vesicular GABA activating synaptic GABAA Rs, is reduced, permitting neurons to appropriately influence the window for postsynaptic excitation...
September 14, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28901728/gaba-type-a-receptor-trafficking-and-the-architecture-of-synaptic-inhibition
#8
REVIEW
Joshua M Lorenz-Guertin, Tija C Jacob
Ubiquitous expression of GABA type A receptors (GABAA R) in the central nervous system establishes their central role in coordinating most aspects of neural function and development. Dysregulation of GABAergic neurotransmission manifests in a number of human health disorders and conditions that in certain cases can be alleviated by drugs targeting these receptors. Precise changes in the quantity or activity of GABAA Rs localized at the cell surface and at GABAergic postsynaptic sites directly impact the strength of inhibition...
September 13, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28901722/%C3%AE-6-subunit-containing-nicotinic-receptors-mediate-low-dose-ethanol-effects-on-ventral-tegmental-area-neurons-and-ethanol-reward
#9
Scott C Steffensen, Samuel I Shin, Ashley C Nelson, Stephanie S Pistorius, Stephanie B Williams, Taylor J Woodward, Hyun Jung Park, Lindsey Friend, Ming Gao, Fenfei Gao, Devin H Taylor, M Foster Olive, Jeffrey G Edwards, Sterling N Sudweeks, Lori M Buhlman, J Michael McIntosh, Jie Wu
Dopamine (DA) neuron excitability is regulated by inhibitory GABAergic synaptic transmission and modulated by nicotinic acetylcholine receptors (nAChRs). The aim of this study was to evaluate the role of α6 subunit-containing nAChRs (α6*-nAChRs) in acute ethanol effects on ventral tegmental area (VTA) GABA and DA neurons. α6*-nAChRs were visualized on GABA terminals on VTA GABA neurons, and α6*-nAChR transcripts were expressed in most DA neurons, but only a minority of VTA GABA neurons from GAD67 GFP mice...
September 13, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28900387/social-isolation-in-early-versus-late-adolescent-mice-is-associated-with-persistent-behavioral-deficits-that-can-be-improved-by-neurosteroid-based-treatment
#10
Andrea Locci, Philippe Geoffroy, Michel Miesch, Ayikoe-Guy Mensah-Nyagan, Graziano Pinna
Early trauma and stress exposure during a critical period of life may increase the risk of major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) in adulthood. The first-choice treatment for MDD and PTSD are selective serotonin reuptake inhibitor (SSRI) antidepressants. Unfortunately, half of MDD and PTSD patients show resistance to the therapeutic effects of these drugs and more efficient treatments are essential. Both MDD and PTSD patients present reduced levels of allopregnanolone (Allo), a potent endogenous positive allosteric modulator of GABA action at GABAA receptors which are normalized by SSRIs in treatment responders...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28900300/rogdi-defines-gabaergic-control-of-a-wake-promoting-dopaminergic-pathway-to-sustain-sleep-in-drosophila
#11
Minjong Kim, Donghoon Jang, Eunseok Yoo, Yangkyun Oh, Jun Young Sonn, Jongbin Lee, Yoonhee Ki, Hyo Jin Son, Onyou Hwang, Changwook Lee, Chunghun Lim, Joonho Choe
Kohlschutter-Tönz syndrome (KTS) is a rare genetic disorder with neurological dysfunctions including seizure and intellectual impairment. Mutations at the Rogdi locus have been linked to development of KTS, yet the underlying mechanisms remain elusive. Here we demonstrate that a Drosophila homolog of Rogdi acts as a novel sleep-promoting factor by supporting a specific subset of gamma-aminobutyric acid (GABA) transmission. Rogdi mutant flies displayed insomnia-like behaviors accompanied by sleep fragmentation and delay in sleep initiation...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899881/tet1-overexpression-leads-to-anxiety-like-behavior-and-enhanced-fear-memories-via-the-activation-of-calcium-dependent-cascade-through-egr1-expression-in-mice
#12
Wookbong Kwon, Hyeng-Soo Kim, Jain Jeong, Yonghun Sung, Minjee Choi, Song Park, Jinhee Lee, Soyoung Jang, Sung Hyun Kim, Sanggyu Lee, Myoung Ok Kim, Zae Young Ryoo
Ten-eleven translocation methylcytosine dioxygenase 1 (Tet1) initiates DNA demethylation by converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) at CpG-rich regions of genes, which have key roles in adult neurogenesis and memory. In addition, the overexpression of Tet1 with 5-hmC alteration in patients with psychosis has also been reported, for instance in schizophrenia and bipolar disorders. The mechanism underlying Tet1 overexpression in the brain; however, is still elusive. In the present study, we found that Tet1-transgenic (Tet1-TG) mice displayed abnormal behaviors involving elevated anxiety and enhanced fear memories...
September 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28898599/transcriptomic-basis-of-metamorphic-competence-in-the-salt-marsh-dwelling-polychaete-capitella-teleta
#13
Robert Burns, Jan Pechenik
Marine invertebrate larvae typically take hours to weeks after being released into the plankton before becoming "competent" to metamorphose. The mechanisms that govern this transition between the precompetent and metamorphically competent states are unknown. We studied gene expression patterns in precompetent and competent larvae of the salt-marsh-dwelling polychaete worm Capitella teleta (Blake, Grassle & Eckelbarger, 2009)-a species in which precompetent larvae are unusually easy to distinguish from competent larvae-to determine differences in gene expression associated with the onset of metamorphic competence...
June 2017: Biological Bulletin
https://www.readbyqxmd.com/read/28894435/neuroactive-steroids-receptor-interactions-and-responses
#14
REVIEW
Kald Beshir Tuem, Tesfay Mehari Atey
Neuroactive steroids (NASs) are naturally occurring steroids, which are synthesized centrally as de novo from cholesterol and are classified as pregnane, androstane, and sulfated neurosteroids (NSs). NASs modulate many processes via interacting with gamma-aminobutyric acid (GABA), N-methyl-d-aspartate, serotonin, voltage-gated calcium channels, voltage-dependent anion channels, α-adrenoreceptors, X-receptors of the liver, transient receptor potential channels, microtubule-associated protein 2, neurotrophin nerve growth factor, and σ1 receptors...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28894409/the-effect-of-4-hydroxybenzaldehyde-on-the-%C3%AE-aminobutyric-acid-type-a-receptor
#15
COMMENT
Jingli Zhang, Habsah Mohamad, Jia Hui Wong, Muhammad Bilal, Abdul Hadi Bin Ismail, Amelia Jane Lloyd, Abdul Aziz Mohamed Yusoff, Hasnah Osman, Kok Tong Wong, Zamzuri Idris, Jafri Malin Abdullah
The α1β2γ2 subtype of GABAA receptors is the most commonly found GABAA receptor subtype in the mammalian cortex and hippocampus. It is expressed heterologously in the Xenopus laevis oocyte as a α1β2γ2S/L subtype for application as an in vitro model for the screening of compounds that modulate receptor activities. In fact, 4-hydroxybenzaldehyde (4-HB) has been identified as one of the major components in Dendrocalamus asper bamboo shoots in our previous study, and the current study showed that at 101.7 μM, 4-HB significantly reduced the GABA-induced chloride current of GABAA receptors expressed on Xenopus oocytes, indicating a possible GABAergic antagonistic effect at high concentrations...
March 2017: Malaysian Journal of Medical Sciences: MJMS
https://www.readbyqxmd.com/read/28890689/integration-between-glycolysis-and-glutamate-glutamine-cycle-flux-may-explain-preferential-glycolytic-increase-during-brain-activation-requiring-glutamate
#16
REVIEW
Leif Hertz, Ye Chen
The 1988 observation by Fox et al. (1988) that brief intense brain activation increases glycolysis (pyruvate formation from glucose) much more than oxidative metabolism has been abundantly confirmed. Specifically glycolytic increase was unexpected because the amount of ATP it generates is much smaller than that formed by subsequent oxidative metabolism of pyruvate. The present article shows that preferential glycolysis can be explained by metabolic processes associated with activation of the glutamate-glutamine cycle...
2017: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/28890150/antagonizing-the-gabaa-receptor-during-behavioral-training-improves-spatial-memory-at-different-doses-in-control-and-chronically-stressed-rats
#17
Kenji J Nishimura, J Bryce Ortiz, Cheryl D Conrad
Chronic stress leads to a dysregulated inhibitory tone that could impact hippocampal-dependent spatial learning and memory. The present study examined whether spatial memory deficits resulting from chronic stress could be overcome by antagonizing the GABAA receptor, a prominent inhibitory receptor of GABA in the hippocampus. Young adult male Sprague-Dawley rats were chronically stressed (STR, wire mesh restraint, 6h/d/21d) or placed in a no-stress control group (CON). When chronic restraint ended, rats were tested on a 2-trial object placement (OP) task at a delay (3hr) that would result in chance performance without intervention and then on novel object recognition (NOR) and the elevated plus maze (EPM) to assess non-spatial memory and anxiety profile...
September 7, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28888841/implications-of-the-n-terminal-heterogeneity-for-the-neuronal-k-cl-cotransporter-kcc2-function
#18
Marika Markkanen, Anastasia Ludwig, Stanislav Khirug, Evgeny Pryazhnikov, Shetal Soni, Leonard Khiroug, Eric Delpire, Claudio Rivera, Matti S Airaksinen, Pavel Uvarov
The neuron-specific K-Cl cotransporter KCC2 maintains the low intracellular chloride concentration required for the fast hyperpolarizing responses of the inhibitory neurotransmitters γ-aminobutyric acid (GABA) and glycine. The two KCC2 isoforms, KCC2a and KCC2b differ by their N-termini as a result of alternative promoter usage. Whereas the role of KCC2b in mediating the chloride transport is unequivocal, the physiological role of KCC2a in neurons has remained obscure. We show that KCC2a isoform can decrease the intracellular chloride concentration in cultured neurons and attenuate calcium responses evoked by application of the GABAA receptor agonist muscimol...
September 6, 2017: Brain Research
https://www.readbyqxmd.com/read/28888448/effect-of-explosion-puffed-coffee-on-locomotor-activity-and-behavioral-patterns-in-drosophila-melanogaster
#19
Bong Soo Ko, So Hyun Ahn, Dong Ouk Noh, Ki-Bae Hong, Sung Hee Han, Hyung Joo Suh
We hypothesized that the administration of explosion-puffed coffee, containing γ-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP), would be associated with a reduction of the caffeine effect on sleep behavior and behavioral patterns, which was investigated in a Drosophila model. The effects of feeding roasted coffee beans (RB), explosion-puffed coffee beans puffed at 0.75MPa and 0.9MPa (PB 7.5 and PB 9.0, respectively), or decaffeinated coffee beans (DeRB) on locomotor activity and behavioral patterns of Drosophila was analyzed...
October 2017: Food Research International
https://www.readbyqxmd.com/read/28881444/gabaergic-inhibition-gates-excitatory-ltp-in-perirhinal-cortex
#20
Vibhakar C Kotak, Ana Mirallave, Todd M Mowery, Dan H Sanes
The perirhinal cortex (PRh) is a key region downstream of auditory cortex (ACx) that processes familiarity linked mnemonic signaling. In gerbils, ACx-driven EPSPs recorded in PRh neurons are largely shunted by GABAergic inhibition (Kotak et al. 2015). To determine whether inhibitory shunting prevents the induction of excitatory long-term potentiation (e-LTP), we stimulated ACx-recipient PRh in a brain slice preparation using theta burst stimulation (TBS). Under control conditions, without GABA blockers, the majority of PRh neurons exhibited long-term depression...
September 7, 2017: Hippocampus
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