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Excitatory glutamate receptors

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https://www.readbyqxmd.com/read/29156239/examining-the-effects-of-alcohol-on-gabaa-receptor-mrna-expression-and-function-in-neural-cultures-generated-from-control-and-alcohol-dependent-donor-induced-pluripotent-stem-cells
#1
Richard Lieberman, Henry R Kranzler, Eric S Levine, Jonathan Covault
Factors influencing the development of alcohol-use disorder (AUD) are complex and heterogeneous. While animal models have been crucial to identifying actions of alcohol on neural cells, human-derived in vitro systems that reflect an individual's genetic background hold promise in furthering our understanding of the molecular and functional effects of alcohol exposure and the pathophysiology of AUD. In this report, we utilized induced pluripotent stem cell (iPSCs)-derived neural cell cultures obtained from healthy individuals (CTLs) and those with alcohol dependence (ADs) to 1) examine the effect of 21-day alcohol exposure on mRNA expression of three genes encoding GABAA receptor subunits (GABRA1, GABRG2, and GABRD) using quantitative PCR, and 2) examine the effect of acute and chronic alcohol exposure on GABA-evoked currents using whole-cell patch-clamp electrophysiology...
August 12, 2017: Alcohol
https://www.readbyqxmd.com/read/29154812/under-stressful-conditions-activation-of-the-ionotropic-p2x7-receptor-differentially-regulates-gaba-and-glutamate-release-from-nerve-terminals-of-the-rat-cerebral-cortex
#2
Aurora R Barros-Barbosa, Ângela Oliveira, M Graça Lobo, J Miguel Cordeiro, Paulo Correia-de-Sá
γ-Aminobutyric acid (GABA) and glutamate (Glu) are the main inhibitory and excitatory neurotransmitters in the central nervous system (CNS), respectively. Fine tuning regulation of extracellular levels of these amino acids is essential for normal brain activity. Recently, we showed that neocortical nerve terminals from patients with epilepsy express higher amounts of the non-desensitizing ionotropic P2X7 receptor. Once activated by ATP released from neuronal cells, the P2X7 receptor unbalances GABAergic vs...
November 14, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29152855/kinase-interest-you-in-treating-incubated-cocaine-craving-a-hypothetical-model-for-treatment-intervention-during-protracted-withdrawal-from-cocaine
#3
REVIEW
Karen K Szumlinski, Christina B Shin
A diagnostic criterion for drug addiction, persistent drug-craving continues to be the most treatment-resistant aspect of addiction that maintains the chronic, relapsing, nature of this disease. Despite the high prevalence of psychomotor stimulant addiction, there currently exists no FDA-approved medication for craving reduction. In good part, this reflects our lack of understanding of the neurobiological underpinnings of drug-craving. In humans, cue-elicited drug-craving is associated with the hyper-excitability of prefrontal cortical regions...
November 20, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29146949/a-microfluidic-platform-for-the-characterisation-of-cns-active-compounds
#4
Christopher MacKerron, Graham Robertson, Michele Zagnoni, Trevor J Bushell
New in vitro technologies that assess neuronal excitability and the derived synaptic activity within a controlled microenvironment would be beneficial for the characterisation of compounds proposed to affect central nervous system (CNS) function. Here, a microfluidic system with computer controlled compound perfusion is presented that offers a novel methodology for the pharmacological profiling of CNS acting compounds based on calcium imaging readouts. Using this system, multiple applications of the excitatory amino acid glutamate (10 nM-1 mM) elicited reproducible and reversible transient increases in intracellular calcium, allowing the generation of a concentration response curve...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29143330/short-term-high-fat-diet-primes-excitatory-synapses-for-long-term-depression-in-orexin-neurons
#5
Victoria Linehan, Lisa Fang, Michiru Hirasawa
Overconsumption of high-fat diets is one of the strongest contributing factors to the rise of obesity rates. Orexin neurons are known to be activated by palatable high-fat diet and mediate the activation of the mesolimbic reward pathway, resulting in further food intake. While short-term exposure to high-fat diet is known to induce synaptic plasticity within the mesolimbic pathway, it is unknown if such changes occur in orexin neurons. To investigate this, 3-week old male rats were fed a palatable high-fat western diet (WD) or control chow for 1 week and then in vitro patch clamp recording was performed...
November 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29140675/identification-of-novel-allosteric-modulators-of-glutamate-transporter-eaat2
#6
Sandhya Kortagere, Ole Valente Mortensen, Jingsheng Xia, William Lester, Yuhong Fang, Yellamelli V V Srikanth, Joseph M Salvino, Andreia Cristina Karklin Fontana
Dysfunction of excitatory amino acid transporters (EAATs) has been implicated in the pathogenesis of various neurological disorders, such as stroke, brain trauma, epilepsyand neurodegenerative diseases among others. EAAT2 is the main subtype responsible for glutamate clearance in the brain, having a key role in regulating transmission and preventing excitotoxicity. Therefore, compounds that increase the expression or activity of EAAT2 have therapeutic potential for neuroprotection. Previous studies identified molecular determinants for EAAT2 transport stimulation in a structural domain that lies at the interface of the rigid trimerization domain and the central substrate binding transport domain...
November 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29133852/nitrosynapsin-therapy-for-a-mouse-mef2c-haploinsufficiency-model-of-human-autism
#7
Shichun Tu, Mohd Waseem Akhtar, Rosa Maria Escorihuela, Alejandro Amador-Arjona, Vivek Swarup, James Parker, Jeffrey D Zaremba, Timothy Holland, Neha Bansal, Daniel R Holohan, Kevin Lopez, Scott D Ryan, Shing Fai Chan, Li Yan, Xiaofei Zhang, Xiayu Huang, Abdullah Sultan, Scott R McKercher, Rajesh Ambasudhan, Huaxi Xu, Yuqiang Wang, Daniel H Geschwind, Amanda J Roberts, Alexey V Terskikh, Robert A Rissman, Eliezer Masliah, Stuart A Lipton, Nobuki Nakanishi
Transcription factor MEF2C regulates multiple genes linked to autism spectrum disorder (ASD), and human MEF2C haploinsufficiency results in ASD, intellectual disability, and epilepsy. However, molecular mechanisms underlying MEF2C haploinsufficiency syndrome remain poorly understood. Here we report that Mef2c (+/-)(Mef2c-het) mice exhibit behavioral deficits resembling those of human patients. Gene expression analyses on brains from these mice show changes in genes associated with neurogenesis, synapse formation, and neuronal cell death...
November 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29123470/regulation-of-ampa-receptor-trafficking-by-protein-ubiquitination
#8
REVIEW
Jocelyn Widagdo, Sumasri Guntupalli, Se E Jang, Victor Anggono
The molecular mechanisms underlying plastic changes in the strength and connectivity of excitatory synapses have been studied extensively for the past few decades and remain the most attractive cellular models of learning and memory. One of the major mechanisms that regulate synaptic plasticity is the dynamic adjustment of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor content on the neuronal plasma membrane. The expression of surface AMPA receptors (AMPARs) is controlled by the delicate balance between the biosynthesis, dendritic transport, exocytosis, endocytosis, recycling and degradation of the receptors...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29120926/recent-insights-into-biological-functions-of-mammalian-bombesin-like-peptides-and-their-receptors
#9
Xiangping Qu, Hui Wang, Rujiao Liu
PURPOSE OF REVIEW: The current review highlights recent advances in physiological and pharmacological researches in biology of mammalian bombesin-like peptides (BLPs). RECENT FINDINGS: BLPs and their receptors were found to have regulatory roles in many biological processes in central nervous system. Two BLPs, neuromedin B and gastrin-releasing peptide (GRP), and their receptors are required for regulation of basal and induced sighing activity in rodents. This is the first study demonstrating central pathways involved in regulation of sighing activity...
November 7, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/29118020/viscerosensory-input-drives-angiotensin-ii-type-1a-receptor-expressing-neurons-in-the-solitary-tract-nucleus
#10
David A Carter, Haoyao Guo, Angela A Connelly, Jaspreet K Bassi, Angelina Y Fong, Andrew Mark Allen, Stuart James McDougall
Homeostatic regulation of visceral organ function requires integrated processing of neural and neurohormonal sensory signals. The nucleus of the solitary tract (NTS) is the primary sensory nucleus for cranial visceral sensory afferents. Angiotensin II (Ang II) is known to modulate peripheral visceral reflexes, in part, by activating Ang II type 1A receptors (AT1AR) in the NTS. AT1AR-expressing NTS neurons occur throughout the NTS with a defined sub-nuclear distribution and most of these neurons are depolarized by Ang II...
November 8, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29118000/ca-2-calmodulin-binding-to-psd-95-mediates-homeostatic-synaptic-scaling-down
#11
Dhrubajyoti Chowdhury, Matthew Turner, Tommaso Patriarchi, Anne C Hergarden, David Anderson, Yonghong Zhang, Junqing Sun, Chao-Yin Chen, James B Ames, Johannes W Hell
Postsynaptic density protein-95 (PSD-95) localizes AMPA-type glutamate receptors (AMPARs) to postsynaptic sites of glutamatergic synapses. Its postsynaptic displacement is necessary for loss of AMPARs during homeostatic scaling down of synapses. Here, we demonstrate that upon Ca(2+) influx, Ca(2+)/calmodulin (Ca(2+)/CaM) binding to the N-terminus of PSD-95 mediates postsynaptic loss of PSD-95 and AMPARs during homeostatic scaling down. Our NMR structural analysis identified E17 within the PSD-95 N-terminus as important for binding to Ca(2+)/CaM by interacting with R126 on CaM...
November 8, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29117230/two-color-one-photon-uncaging-of-glutamate-and-gaba
#12
Stefan Passlick, Paul F Kramer, Matthew T Richers, John T Williams, Graham C R Ellis-Davies
Neuronal cells receive a variety of excitatory and inhibitory signals which they process to generate an output signal. In order to study the interaction between excitatory and inhibitory receptors with exogenously applied transmitters in the same preparation, two caging chromophores attached to glutamate and GABA were developed that were selectively photolyzed by different wavelengths of light. This technique has the advantage that the biologically inactive caged compound can be applied at equilibrium prior to the near instantaneous release of the transmitters...
2017: PloS One
https://www.readbyqxmd.com/read/29112734/memantine-prevents-acute-radiation-induced-toxicities-at-hippocampal-excitatory-synapses
#13
Joseph G Duman, Jeffrey Dinh, Wei Zhou, Henry Cham, Vasilis C Mavratsas, Matea Paveškovic, Shalaka Mulherkar, Susan L McGovern, Kimberley F Tolias, David R Grosshans
Background: Memantine has shown clinical utility in preventing radiation-induced cognitive impairment, but the mechanisms underlying its protective effects remain unknown. We hypothesized that abnormal glutamate signaling causes radiation-induced abnormalities in neuronal structure and that memantine prevents synaptic toxicity. Methods: Hippocampal cultures expressing eGFP were irradiated or sham-treated and their dendritic spine morphology assessed at acute (minutes) and later (days) times using high-resolution confocal microscopy...
November 2, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29098176/transient-prepubertal-mifepristone-treatment-normalizes-deficits-in-contextual-memory-and-neuronal-activity-of-adult-male-rats-exposed-to-maternal-deprivation
#14
Manila Loi, Ratna Angela Sarabdjitsingh, Andromachi Tsouli, Stephanie Trinh, Marit Arp, Harmen J Krugers, Henk Karst, Ruud van den Bos, Marian Joëls
Early life adversity is a well-known risk factor for behavioral dysfunction later in life, including the formation of contextual memory; it is also (transiently) accompanied by hyperactivity of the stress system. We tested whether mifepristone (MIF) treatment, which among other things blocks glucocorticoid receptors (GRs), during the prepubertal period [postnatal days (PND)26-PND28] normalizes memory deficits in adult male rats exposed to 24-h maternal deprivation (MD) at PND3. MD reduced body weight gain and increased basal corticosterone (CORT) levels during the PND26, but not in adulthood...
September 2017: ENeuro
https://www.readbyqxmd.com/read/29089052/epigenetic-control-of-epilepsy-target-genes-contributes-to-a-cellular-memory-of-epileptogenesis-in-cultured-rat-hippocampal-neurons
#15
K Kiese, J Jablonski, J Hackenbracht, J K Wrosch, T W Groemer, J Kornhuber, I Blümcke, K Kobow
Hypersynchronous neuronal excitation manifests clinically as seizure (ictogenesis), and may recur spontaneously and repetitively after a variable latency period (epileptogenesis). Despite tremendous research efforts to describe molecular pathways and signatures of epileptogenesis, molecular pathomechanisms leading to chronic epilepsy remain to be clarified. We hypothesized that epigenetic modifications may form the basis for a cellular memory of epileptogenesis, and used a primary neuronal cell culture model of the rat hippocampus to study the translation of massive neuronal excitation into persisting changes of epigenetic signatures and pro-epileptogenic target gene expression...
October 31, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29075178/regulation-of-hippocampal-5-ht-release-by-p2x7-receptors-in-response-to-optogenetic-stimulation-of-median-raphe-terminals-of-mice
#16
Flóra Gölöncsér, Mária Baranyi, Diána Balázsfi, Kornél Demeter, József Haller, Tamás F F Freund, Dóra Zelena, Beáta Sperlágh
Serotonergic and glutamatergic neurons of median raphe region (MRR) play a pivotal role in the modulation of affective and cognitive functions. These neurons synapse both onto themselves and remote cortical areas. P2X7 receptors (P2rx7) are ligand gated ion channels expressed by central presynaptic excitatory nerve terminals and involved in the regulation of neurotransmitter release. P2rx7s are implicated in various neuropsychiatric conditions such as schizophrenia and depression. Here we investigated whether 5-HT release released from the hippocampal terminals of MRR is subject to modulation by P2rx7s...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29074619/presynaptic-mglur5-receptor-controls-glutamatergic-input-through-protein-kinase-c-nmda-receptors-in-paclitaxel-induced-neuropathic-pain
#17
Jing-Dun Xie, Shao-Rui Chen, Hui-Lin Pan
Chemotherapeutic drugs such as paclitaxel cause painful peripheral neuropathy in many cancer patients and survivors. Although NMDA receptors (NMDARs) at primary afferent terminals are known to be critically involved in chemotherapy-induced chronic pain, the upstream signaling mechanism that leads to presynaptic NMDAR activation is unclear. Group I metabotropic glutamate receptors (mGluRs) play a role in synaptic plasticity and NMDAR regulation. Here we report that the Group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) significantly increased the frequency of miniature excitatory postsynaptic currents (EPSCs) and the amplitude of monosynaptic EPSCs evoked from the dorsal root...
October 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29071893/-influence-of-electroacupuncture-intervention-on-glutamic-acid-and-ca-2-contents-and-expression-of-nmda-receptor-protein-in-hippocampus-in-vascular-dementia-rats
#18
Qian Zhang, Chuang Zhang, Jia-Yin Zhang, Hui-Zhen Zhang, Xiao-Feng Li, Hong-Ling Xiao, Yan-Hui Sun, Hai-Jiao Xing, Xiao-Kang Xu, Yu-Lei Liang, Xin Zhang, Xiao-Qi Zhang, Ai-Ying Li
OBJECTIVE: To observe the influence of electroacupuncture (EA) intervention on hippocampal glutamate (Glu) and Ca(2+) contents, and expression of Glu-N-methyl-D-aspartic acid receptor(NMDAR) and the learning-memory ability in vascular dementia (VD) rats, so as to reveal its mechanisms underlying improvement of VD. METHODS: SD rats were rando-mized into sham operation (sham) group (n=9), model group (n=11) and EA groups (n=10). The VD model was established by repeated bilateral common carotid arteries occlusion and reperfusion plus intraperitoneal injection of sodium nitroprusside...
December 25, 2016: Zhen Ci Yan Jiu, Acupuncture Research
https://www.readbyqxmd.com/read/29066956/cell-type-specific-expression-of-corticotropin-releasing-hormone-binding-protein-in-gabaergic-interneurons-in-the-prefrontal-cortex
#19
Kyle D Ketchesin, Nicholas S Huang, Audrey F Seasholtz
Corticotropin-releasing hormone-binding protein (CRH-BP) is a secreted glycoprotein that binds CRH with very high affinity to modulate CRH receptor activity. CRH-BP is widely expressed throughout the brain, with particularly high expression in regions such as the amygdala, hippocampus, ventral tegmental area and prefrontal cortex (PFC). Recent studies suggest a role for CRH-BP in stress-related psychiatric disorders and addiction, with the PFC being a potential site of interest. However, the molecular phenotype of CRH-BP-expressing cells in this region has not been well-characterized...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/29065265/energetics-of-glutamate-binding-to-an-ionotropic-glutamate-receptor
#20
Alvin Yu, Albert Y Lau
Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that are responsible for the majority of excitatory transmission at the synaptic cleft. Mechanically speaking, agonist binding to the ligand binding domain (LBD) activates the receptor by triggering a conformational change that is transmitted to the transmembrane region, opening the ion channel pore. We use fully atomistic molecular dynamics simulations to investigate the binding process in the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, an iGluR subtype...
November 9, 2017: Journal of Physical Chemistry. B
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