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kainate receptor

John J Marshall, Jian Xu, Anis Contractor
Kainate receptors are members of the glutamate receptor family that function both by generating ionotropic currents through an integral ion channel pore, and through coupling to downstream metabotropic signaling pathways. They are highly expressed in the striatum yet their roles in regulating striatal synapses are not known. Using mice of both sexes we demonstrate that GluK2 containing kainate receptors expressed in direct pathway Spiny Projection Neurons (dSPNs) inhibit glutamate release at corticostriatal synapses in the dorsolateral striatum...
March 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
M P García-Pardo, J Miñarro, M A Aguilar
Currently, there is not an effective treatment for 3,4-methylenedioxymethamphetamine (MDMA) dependence but pharmacotherapies targeting glutamate neurotransmission are a promising strategy. Previously, we showed that blockade of glutamate NMDA and AMPA receptors impairs the conditioned rewarding effects of MDMA and cocaine, respectively. In this study we evaluated the role of AMPA receptors in the rewarding effects of MDMA in mice using the conditioned place preference (CPP) paradigm. Mice were conditioned with MDMA (1,25 mg/kg) 60 min after the treatment with saline or different doses (0,25, 1 and 5 mg/kg) of the AMPA/kainate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)...
March 8, 2018: Behavioural Brain Research
Hideki Takago, Tomoko Oshima-Takago
The ionotropic glutamate receptors (iGluRs) concertedly mediate neurotransmission to convey, process, and integrate acoustic information along the auditory pathway. In order to ensure these challenging tasks, the iGluRs are variously expressed in auditory neurons in an age- and site-dependent manner. The subunit compositions of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs) are altered with development, underlying the acceleration in kinetics of excitatory postsynaptic responses...
February 28, 2018: Hearing Research
N S Makara, T A Sapozhnikova, R Yu Khisamutdinova, I P Tsypysheva, S S Borisevich, A V Kovalskaya, P R Petrova, C L Khursan, F S Zarudii
We performed screening of nootropic properties of 10 new derivatives of quinolizidine alkaloid (-)-cytisine. Compounds with β-endo stereochemistry were more active than α-endo-isomers. Under stress conditions (3aR,4S,8S,12R,12aS,12bR)-10-methyl-2-phenyloctahydro-1H-4,12a-etheno-8,12-methanopyrrolo[3',4':3,4]pyrido[1,2-a] [1,5]diazocine-1,3,5(4H)-trione enhanced memory and had a positive effect on cognitive functions of rats. According to molecular docking data, the nootropic activity of the compound can be associated with its affinity for the glutamate-binding subunits GluK1 and GluR2 of the kainate and AMPA receptor, respectively...
March 3, 2018: Bulletin of Experimental Biology and Medicine
Sheela Verjee, Anna Weston, Christiane Kolb, Heba Kalbhenn-Aziz, Veronika Butterweck
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis plays an important part in the development of depressive symptoms. In this study, the effects of a commercial St. John's wort extract (STW3-VI), hyperforin, miquelianin, and the selective serotonin reuptake inhibitor citalopram on the expression of genes relevant to HPA axis function were investigated in human neuronal cells. SH-SY5Y cells were treated with STW3-VI (20 µg/mL), hyperforin (1 µM), miquelianin (10 µM), or citalopram (10 µM) in the presence of the glucocorticoid receptor agonist dexamethasone (DEX,10 µM) for 6 h and 48 h, respectively...
March 2, 2018: Planta Medica
Hea Nam Hong, Ju Hee Shim, You Jin Won, Jong Yoon Yoo, Chang Ho Hwang
BACKGROUND: The objective of this study was to investigate the underlying molecular mechanisms and the therapeutic time window for preventing astrogliosis with erythropoietin (EPO) treatment after in vitro modeled spinal cord injury (SCI). METHODS: Cultured rat spinal cord astrocytes were treated with kainate and scratching to generate an in vitro model of SCI. EPO (100U/mL or 300U/mL) was added immediately or 2, 4, or 8 hours after injury. Some cultures were also treated with AG490, an inhibitor of the EPO-EPO receptor (EpoR) pathway mediator Janus kinase 2 (JAK2)...
March 2018: Medicine (Baltimore)
Simone Brogi, Margherita Brindisi, Stefania Butini, Giridhar Uttam Kshirsagar, Samuele Maramai, Giulia Chemi, Sandra Gemma, Giuseppe Campiani, Ettore Novellino, Paolo Fiorenzani, Jessica Pinassi, Anna Maria Aloisi, Mikko Gynther, Raminta Venskutonyte, Liwei Han, Karla Frydenvang, Jette Sandholm Kastrup, Darryl S Pickering
Starting from 1-4 and 7 structural templates, analogues based on bioisosteric replacements (5a-c vs 1, 2 and 6 vs 7) were synthesized for completing the SAR analysis. Interesting binding properties at GluA2, GluK1 and GluK3 receptors were discovered. The requirements for GluK3 interaction were elucidated determining the X-ray structures of the GluK3-LBD with 2 and 5c and by computational studies. Antinociceptive potential was demonstrated for GluK1 partial agonist 3 and antagonist 7 (2 mg/kg ip).
February 16, 2018: Journal of Medicinal Chemistry
James L Butler, Y Audrey Hay, Ole Paulsen
The entorhinal-hippocampal system is an important circuit in the brain, essential for certain cognitive tasks such as memory and navigation. Different gamma oscillations occur in this circuit, with the medial entorhinal cortex (mEC), CA3 and CA1 all generating gamma oscillations with different properties. These three gamma oscillations converge within CA1, where much work has gone into trying to isolate them from each other. Here, we compared the gamma generators in the mEC, CA3 and CA1 using optogenetically induced theta-gamma oscillations...
January 22, 2018: European Journal of Neuroscience
Venkat Swaroop Achuta, Tommi Möykkynen, Ulla-Kaisa Peteri, Giorgio Turconi, Claudio Rivera, Kari Keinänen, Maija L Castrén
Altered neuronal network formation and function involving dysregulated excitatory and inhibitory circuits are associated with fragile X syndrome (FXS). We examined functional maturation of the excitatory transmission system in FXS by investigating the response of FXS patient-derived neural progenitor cells to the glutamate analog (AMPA). Neural progenitors derived from induced pluripotent stem cell (iPSC) lines generated from boys with FXS had augmented intracellular Ca2+ responses to AMPA and kainate that were mediated by Ca2+-permeable AMPA receptors (CP-AMPARs) lacking the GluA2 subunit...
January 16, 2018: Science Signaling
Elisa Landucci, Luca Filippi, Elisabetta Gerace, Serena Catarzi, Renzo Guerrini, Domenico E Pellegrini-Giampietro
Hypoxic-ischemic encephalopathy (HIE) is a major cause of perinatal mortality and subsequent severe neurological sequelae. Mild hypothermia is a standard therapy for HIE, but is used only in selected Reference Centers and in neonates >1800 g. Since neuronal death following HIE occurs by a cascade of events triggered by activation of glutamate receptors, we used in vitro and in vivo models of HIE to examine whether the AMPA/kainate receptor antagonist topiramate and the NMDA receptor antagonist memantine could exert neuroprotective effects, alone or in combination with hypothermia...
January 12, 2018: Neuroscience Letters
Daniel P Radin, Yong-Xin Li, Gary Rogers, Richard Purcell, Arnold Lippa
It was previously reported that Stargazin (STG) enhances the surface expression of AMPA receptors, controls receptor gating and slows channel desensitization as an auxiliary subunit of the receptors. Ampakines are a class of AMPA receptor positive allosteric modulators that modify rates of transmitter binding, channel activity and desensitization parameters. As such, they have shown efficacy in animal models of neurodegenerative diseases, where excitatory synaptic transmission is compromised. Given the functional similarities between STG and ampakines, the current study sought to probe interactions between STG and ampakine gating properties...
January 9, 2018: Biochemical Pharmacology
Jana Ruda-Kucerova, Zuzana Babinska, Matej Luptak, Bruk Getachew, Yousef Tizabi
The devastating consequences of alcohol-use disorder (AUD) on the individual and the society are well established. Current treatments of AUD encompass various strategies, all of which have only modest effectiveness. Hence, there is a critical need to develop more efficacious therapies. Recently, specific glutamatergic receptors have been identified as potential novel targets for intervention in AUD. Thus, the current study was designed to evaluate the effects of acute administration of sub-anesthetic doses of ketamine, an NMDA receptor antagonist, as well as NBQX, an AMPA/kainate receptor antagonist on alcohol intake and its possible behavioural consequences...
December 27, 2017: Neuroscience Letters
Xu-Hui Li, Qian Song, Qi-Yu Chen, Jing-Shan Lu, Tao Chen, Min Zhuo
The tree shrew, as a primate-like animal model, has been used for studying high brain functions such as social emotion and spatial learning memory. However, little is known about the excitatory synaptic transmission in cortical brain areas of the tree shrew. In the present study, we have characterized the excitatory synaptic transmission and intrinsic properties of pyramidal neurons in the anterior cingulate cortex (ACC) of the adult tree shrew, a key cortical region for pain perception and emotion. We found that glutamate is the major excitatory transmitter for fast synaptic transmission...
December 18, 2017: Molecular Brain
Maria Koromina, Miles Flitton, Ian Mellor, Helen Miranda Knight
OBJECTIVES: Cognitive deficits are a common feature of neuropsychiatric disorders. We investigated the relationship between cognitive performance and a deletion allele within GluK4 protective against risk for bipolar disorder, in 1642 individuals from the TwinsUK study. METHODS: Cognitive performance was assessed using the National Adult Reading Test, four CANTAB tests (Spatial Working Memory, Paired Associates Learning, Pattern Recognition Memory, and Reaction Time), and two Principal Component Analysis derived factors...
December 15, 2017: World Journal of Biological Psychiatry
Vanessa M Lopes, Rui Rosa, Pedro R Costa
Domoic acid (DA) is a neurotoxin that causes degenerative damage to brain cells and induces permanent short-term memory loss in mammals. In cephalopod mollusks, although DA is known to accumulate primarily in the digestive gland, there is no knowledge whether DA reaches their central nervous system. Here we report, for the first time, the presence of DA in brain tissue of the common octopus (Octopus vulgaris) and the European cuttlefish (Sepia officinalis), and its absence in the brains of several squid species (Loligo vulgaris, L...
February 2018: Marine Environmental Research
Dimitrinka Atanasova, Jana Tchekalarova, Natasha Ivanova, Zlatina Nenchovska, Ekaterina Pavlova, Nina Atanassova, Nikolai Lazarov
AIMS: Experimental and clinical studies have demonstrated that components of renin-angiotensin system are elevated in the hippocampus in epileptogenic conditions. In the present work, we explored the changes in the expression of angiotensin II receptor, type 1 (AT1 receptor) in limbic structures, as well as the effect of the AT1 receptor antagonist losartan in a model of comorbid hypertension and epilepsy. MAIN METHODS: The expression of AT1 receptors was compared between spontaneously hypertensive rats (SHRs) and Wistar rats by using immunohistochemistry in the kainate (KA) model of temporal lobe epilepsy (TLE)...
January 15, 2018: Life Sciences
Tristan P Hedrick, William P Nobis, Kendall M Foote, Toshiyuki Ishii, Dane M Chetkovich, Geoffrey T Swanson
Hilar mossy cells (HMCs) in the hippocampus receive glutamatergic input from dentate granule cells (DGCs) via mossy fibers (MFs) and back-projections from CA3 pyramidal neuron collateral axons. Many fundamental features of these excitatory synapses have not been characterized in detail despite their potential relevance to hippocampal cognitive processing and epilepsy-induced adaptations in circuit excitability. In this study, we compared pre- and postsynaptic parameters between MF and CA3 inputs to HMCs in young and adult mice of either sex and determined the relative contributions of the respective excitatory inputs during in vitro and in vivo models of hippocampal hyperexcitability...
November 2017: ENeuro
Shaunik Sharma, Steven Carlson, Sreekanth Puttachary, Souvarish Sarkar, Lucas Showman, Marson Putra, Anumantha G Kanthasamy, Thimmasettappa Thippeswamy
Status epilepticus (SE) induces neuroinflammation and epileptogenesis, but the mechanisms are not yet fully delineated. The Fyn, a non-receptor Src family tyrosine kinase (SFK), and its immediate downstream target, PKCδ are emerging as potential mediators of neuroinflammation. In order to first determine the role of Fyn kinase signaling in SE, we tested the efficacy of a SFK inhibitor, saracatinib (25mg/kg, oral) in C57BL/6J mouse kainate model of acute seizures. Saracatinib pretreatment dampened SE severity and completely prevented mortality...
February 2018: Neurobiology of Disease
Zahra Abedi, Huzwah Khaza'ai, Sharmili Vidyadaran, Mohd Sokhini Abd Mutalib
Astrocytes are known as structural and supporting cells in the central nervous system (CNS). Glutamate, as a main excitatory amino acid neurotransmitter in the mammalian central nervous system, can be excitotoxic, playing a key role in many chronic neurodegenerative diseases. The aim of the current study was to elucidate the potential of vitamin E in protecting glutamate-injured primary astrocytes. Hence, primary astrocytes were isolated from mixed glial cells of C57BL/6 mice by applying the EasySep® Mouse CD11b Positive Selection Kit, cultured in Dulbecco's modified Eagle medium (DMEM) and supplemented with special nutrients...
December 1, 2017: Biomedicines
Linxiao Wang, Yanyan Liu, Rulan Lu, Guoying Dong, Xia Chen, Wenwei Yun, Xianju Zhou
Epilepsy is a chronic brain disease affecting millions of individuals. Kainate receptors, especially kainate-type of ionotropic glutamate receptor 2 (GluK2), play an important role in epileptogenesis. Recent data showed that GluK2 could undergo post-translational modifications in terms of S-nitrosylation (SNO), and affect the signaling pathway of cell death in cerebral ischemia-reperfusion. However, it is unclear whether S-nitrosylation of GluK2 (SNO-GluK2) contributes to cell death induced by epilepsy. Here, we report that kainic acid-induced SNO-GluK2 is mediated by GluK2 itself, regulated by neuronal nitric oxide synthase (nNOS) and the level of cytoplasmic calcium in vivo and in vitro hippocampus neurons...
February 2018: Journal of Neurochemistry
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