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https://www.readbyqxmd.com/read/28916627/interactions-between-medial-prefrontal-cortex-and-dorsomedial-striatum-are-necessary-for-odor-span-capacity-in-rats-role-of-glun2b-containing-nmda-receptors
#1
Don A Davies, Quentin Greba, Jantz C Selk, Jillian K Catton, Landon D Baillie, Sean J Mulligan, John G Howland
Working memory is involved in the maintenance and manipulation of information essential for complex cognition. While the neural substrates underlying working memory capacity have been studied in humans, considerably less is known about the circuitry mediating working memory capacity in rodents. Therefore, the present experiments tested the involvement of medial prefrontal cortex (mPFC) and dorsal striatum (STR) in the odor span task (OST), a task proposed to assay working memory capacity in rodents. Initially, Long Evans rats were trained to dig in scented sand for food following a serial delayed nonmatching-to-sample rule...
October 2017: Learning & Memory
https://www.readbyqxmd.com/read/28916251/mk-801-but-not-naloxone-attenuates-high-dose-dextromethorphan-induced-convulsive-behavior-possible-involvement-of-the-glun2b-receptor
#2
Hai-Quyen Tran, Yoon Hee Chung, Eun-Joo Shin, The-Vinh Tran, Ji Hoon Jeong, Choon-Gon Jang, Seung-Yeol Nah, Kiyofumi Yamada, Toshitaka Nabeshima, Hyoung-Chun Kim
Dextromethorphan (DM) is a dextrorotatory isomer of levorphanol, a typical morphine-like opioid. When administered at supra-antitussive doses, DM produces psychotoxic and neurotoxic effects in humans. Although DM abuse has been well-documented, few studies have examined the effects of high-dose DM. The present study aimed to explore the effects of a single high dose of DM on mortality and seizure occurrence. After intraperitoneal administration with a high dose of DM (80mg/kg), Sprague-Dawley rats showed increased seizure occurrence and intensity...
September 12, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28912687/alterations-in-properties-of-glutamatergic-transmission-in-the-temporal-cortex-and-hippocampus-following-pilocarpine-induced-acute-seizures-in-wistar-rats
#3
Dmitry V Amakhin, Sergey L Malkin, Julia L Ergina, Kirill A Kryukov, Ekaterina A Veniaminova, Olga E Zubareva, Aleksey V Zaitsev
Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy in humans, and is often developed after an initial precipitating brain injury. This form of epilepsy is frequently resistant to pharmacological treatment; therefore, the prevention of TLE is the prospective approach to TLE therapy. The lithium-pilocarpine model in rats replicates some of the main features of TLE in human, including the pathogenic mechanisms of cell damage and epileptogenesis after a primary brain injury. In the present study, we investigated changes in the properties of glutamatergic transmission during the first 3 days after pilocarpine-induced acute seizures in Wistar rats (PILO-rats)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28912680/fyn-signaling-is-compartmentalized-to-dopamine-d1-receptor-expressing-neurons-in-the-dorsal-medial-striatum
#4
Khanhky Phamluong, Emmanuel Darcq, Su Wu, Samuel A Sakhai, Dorit Ron
The tyrosine kinase Fyn plays an important role in synaptic plasticity, learning, and memory. Here we report that Fyn is activated in response to 15 min D1 receptor (D1R) but not D2 receptor (D2R) stimulation specifically in the dorsomedial striatum (DMS) of mice but not in the other substriatal regions, the dorsolateral striatum (DLS), and the nucleus accumbens (NAc). Once activated Fyn phosphorylates its substrate GluN2B, and we show that GluN2B is phosphorylated only in the DMS but not in the other striatal regions...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28911960/characterization-of-the-adrenocorticotrophic-hormone-induced-mouse-model-of-resistance-to-antidepressant-drug-treatment
#5
Bettadapura N Srikumar, Mahesh Paschapur, Narasimharaju Kalidindi, Bharath Adepu, Manish L Das, Muppana V Sreedhara, Vijaya K Kuchibhotla, Rick L Pieschl, Yu-Wen Li, Durga Shiva Prasad Ega, Justin Louis, Senthilkumar Murugesan, Pattipati S Naidu, Manjunath Ramarao, Linda J Bristow, Reeba K Vikramadithyan
Approximately 30-60% of patients treated with existing antidepressants fail to achieve remission of depressive symptoms leading to Treatment Resistant Depression (TRD). There is an urgent need to develop novel medications, which is highly limited by the non-availability of relevant animal models with good predictive validity. ACTH administration has been shown to result in the resistance to acute and chronic effects of imipramine. However, the pharmacology of the model and the mechanisms contributing to the resistance are not completely understood...
September 11, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28899992/depletion-of-progranulin-reduces-glun2b-containing-nmda-receptor-density-tau-phosphorylation-and-dendritic-arborization-in-mouse-primary-cortical-neurons
#6
Francesca Longhena, Michela Zaltieri, Jessica Grigoletto, Gaia Faustini, Luca La Via, Roberta Ghidoni, Luisa Benussi, Cristina Missale, PierFranco Spano, Arianna Bellucci
Loss-of-function mutations in the progranulin (PGRN) gene are a common cause of familial frontotemporal lobar degeneration (FTLD). This an age-related neurodegenerative disorder characterized by brain atrophy in the frontal and temporal lobes and with typical symptoms such as cognitive and memory impairment, profound behavioral abnormalities and personality changes, that are thought to be related to connectome dysfunctions. Recently, PGRN reduction has been found to induce a behavioural phenotype reminiscent of FTLD symptoms in mice by affecting neuron spine density and morphology, suggesting that the protein can influence neuronal structural plasticity...
September 12, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28887453/hyaluronic-acid-based-extracellular-matrix-regulates-surface-expression-of-glun2b-containing-nmda-receptors
#7
Barbara Schweitzer, Jeet Singh, Anna Fejtova, Laurent Groc, Martin Heine, Renato Frischknecht
Cortical areas of the juvenile rodent brain display a high degree of structural and functional plasticity, which disappears later in development. Coincident with the decline of plasticity 1) the hyaluronic acid-based extracellular matrix (ECM) of the brain, which stabilizes synapses and neuronal circuit is formed and 2) N-methyl-D-aspartate subtype of ionotropic glutamate receptors (NMDARs) implied in synaptic plasticity switch from mainly GluN2B to GluN2A subunit-containing receptors. Here we tested the hypothesis that ECM influences the NMDAR subunit composition in dissociated neuronal cultures...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28884870/phosphorylated-snap25-in-the-ca1-regulates-morphine-associated-contextual-memory-retrieval-via-increasing-glun2b-nmdar-surface-localization
#8
Xinjuan Wang, Yan Liu, Meng Jia, Xiaowei Sun, Na Wang, Yijing Li, Cailian Cui
Although our previous studies have demonstrated both protein kinase C (PKC) and GluN2B-containing N-methyl-d-aspartate receptor (GluN2B-NMDAR) play crucial roles in morphine-associated learning and memory, the relationship between them remains unexplored. In this study, we validated the enhanced PKC and membrane GluN2B protein expression in the hippocampal CA1 after morphine conditioned place preference (CPP) expression in rats. Interestingly, we also found that phosphorylation of SNAP25 at Ser187 (pSer187-SNAP25), a PKC-activated target, was significantly increased following morphine CPP expression...
September 8, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28878777/zika-virus-promotes-neuronal-cell-death-in-a-non-cell-autonomous-manner-by-triggering-the-release-of-neurotoxic-factors
#9
Isabella G Olmo, Toniana G Carvalho, Vivian V Costa, Juliana Alves-Silva, Carolina Z Ferrari, Tatiane C Izidoro-Toledo, Juliana F da Silva, Antonio L Teixeira, Danielle G Souza, Joao T Marques, Mauro M Teixeira, Luciene B Vieira, Fabiola M Ribeiro
Zika virus (ZIKV) has recently caused a worldwide outbreak of infections associated with severe neurological complications, including microcephaly in infants born from infected mothers. ZIKV exhibits high neurotropism and promotes neuroinflammation and neuronal cell death. We have recently demonstrated that N-methyl-d-aspartate receptor (NMDAR) blockade by memantine prevents ZIKV-induced neuronal cell death. Here, we show that ZIKV induces apoptosis in a non-cell autonomous manner, triggering cell death of uninfected neurons by releasing cytotoxic factors...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28855140/prenatal-stress-induced-gender-specific-alterations-of-n-methyl-d-aspartate-receptor-subunit-expression-and-response-to-a%C3%AE-in-offspring-hippocampal-cells
#10
Yuan Fang, Hui Li, Lirong Chang, Yizhi Song, Longhui Ma, Liying Lu, Zunshu Du, Yan Li, Jinping Liu, Yan Wu
Prenatal stress (PS) is one of adverse life events during pregnancy, which may increase vulnerability to cognitive impairment in adult offspring. Aβ synaptotoxicity is one important pathological factor for cognitive impairment, and PS-induced cognitive disorder is closely associated with N-Methyl-d-Aspartate receptor (NMDAR), which acts as a key mediator of Aβ synaptotoxicity. In the present study, we tried to explore whether PS affects offspring's Aβ levels and NMDAR subunit expression in a gender-specific manner in hippocampal CA and DG subregions, and whether PS affects synaptic proteins and NMDAR subunit expression in cultured offspring hippocampal cells exposed to Aβ...
September 9, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28838956/adenylyl-cyclase-1-is-required-for-ethanol-induced-locomotor-sensitization-and-associated-increases-in-nmda-receptor-phosphorylation-and-function-in-the-dorsal-medial-striatum
#11
Kelly E Bosse, Max F Oginsky, Laura L Susick, Sailesh Ramalingam, Carrie R Ferrario, Alana C Conti
Neuroadaptive responses to chronic ethanol, such as behavioral sensitization, are associated with NMDA receptor (NMDAR) recruitment. Ethanol enhances GluN2B-containing NMDAR function and phosphorylation (Tyr-1472) of the GluN2B-NMDAR subunit in the dorsal medial striatum (DMS) through a protein kinase A (PKA)-dependent pathway. Ethanol-induced phosphorylation of PKA substrates is partially mediated by calcium-stimulated adenylyl cyclase 1 (AC1), which is enriched in the dorsal striatum. As such, AC1 is poised as an upstream modulator of ethanol-induced DMS neuroadaptations that promote drug responding and, thus, represents a therapeutic target...
August 24, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28834750/synaptic-regulation-of-a-thalamocortical-circuit-controls-depression-related-behavior
#12
Oliver H Miller, Andreas Bruns, Imen Ben Ammar, Thomas Mueggler, Benjamin J Hall
The NMDA receptor (NMDAR) antagonist ketamine elicits a long-lasting antidepressant response in patients with treatment-resistant depression. Understanding how antagonism of NMDARs alters synapse and circuit function is pivotal to developing circuit-based therapies for depression. Using virally induced gene deletion, ex vivo optogenetic-assisted circuit analysis, and in vivo chemogenetics and fMRI, we assessed the role of NMDARs in the medial prefrontal cortex (mPFC) in controlling depression-related behavior in mice...
August 22, 2017: Cell Reports
https://www.readbyqxmd.com/read/28829421/electroconvulsive-seizures-in-rats-and-fractionation-of-their-hippocampi-to-examine-seizure-induced-changes-in-postsynaptic-density-proteins
#13
Sung-Soo Jang, Han Gil Jeong, Hee Jung Chung
Electroconvulsive seizure (ECS) is an experimental animal model of electroconvulsive therapy, the most effective treatment for severe depression. ECS induces generalized tonic-clonic seizures with low mortality and neuronal death and is a widely-used model to screen anti-epileptic drugs. Here, we describe an ECS induction method in which a brief 55-mA current is delivered for 0.5 s to male rats 200 - 250 g in weight via ear-clip electrodes. Such bilateral stimulation produced stage 4 - 5 clonic seizures that lasted about 10 s...
August 15, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28821276/inflammatory-demyelination-alters-subcortical-visual-circuits
#14
Sheila Espírito Santo Araújo, Henrique Rocha Mendonça, Natalie A Wheeler, Paula Campello-Costa, Kimberle M Jacobs, Flávia C A Gomes, Michael A Fox, Babette Fuss
BACKGROUND: Multiple sclerosis (MS) is an inflammatory demyelinating disease classically associated with axonal damage and loss; more recently, however, synaptic changes have been recognized as additional contributing factors. An anatomical area commonly affected in MS is the visual pathway; yet, changes other than those associated with inflammatory demyelination of the optic nerve, i.e., optic neuritis, have not been described in detail. METHODS: Adult mice were subjected to a diet containing cuprizone to mimic certain aspects of inflammatory demyelination as seen in MS...
August 18, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28808323/stress-hormone-rapidly-tunes-synaptic-nmda-receptor-through-membrane-dynamics-and-mineralocorticoid-signalling
#15
Lenka Mikasova, Hui Xiong, Amber Kerkhofs, Delphine Bouchet, Harm J Krugers, Laurent Groc
Stress hormones, such as corticosteroids, modulate the transmission of hippocampal glutamatergic synapses and NMDA receptor (NMDAR)-dependent synaptic plasticity, favouring salient behavioural responses to the environment. The corticosterone-induced synaptic adaptations partly rely on changes in NMDAR signalling, although the cellular pathway underlying this effect remains elusive. Here, we demonstrate, using single molecule imaging and electrophysiological approaches in hippocampal neurons, that corticosterone specifically controls GluN2B-NMDAR surface dynamics and synaptic content through mineralocorticoid signalling...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28797770/replacement-of-benzylic-hydroxy-group-by-vinyl-or-hydroxymethyl-moiety-at-the-3-benzazepine-scaffold-retaining-glun2b-affinity
#16
Susann Rath, Dirk Schepmann, Bernhard Wünsch
Since overactivation of NMDA receptors is associated with neurodegenerative disorders, the design and development of subunit-selective NMDA receptor antagonists are of great interest. In order to avoid the formation of quinone-like intermediates as starting point for degradation the benzylic OH group of the lead compounds 2 was replaced by an electron rich vinyl or homologous hydroxymethyl moiety. The Bi(OTf)3 catalyzed intramolecular Friedel-Crafts alkylation of 9a represents the key step in the synthesis of 1-vinyl substituted tetrahydro-3-benzazepine 10...
July 29, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28793260/peripheral-elevation-of-a-klotho-fragment-enhances-brain-function-and-resilience-in-young-aging-and-%C3%AE-synuclein-transgenic-mice
#17
Julio Leon, Arturo J Moreno, Bayardo I Garay, Robert J Chalkley, Alma L Burlingame, Dan Wang, Dena B Dubal
Cognitive dysfunction and decreased mobility from aging and neurodegenerative conditions, such as Parkinson and Alzheimer diseases, are major biomedical challenges in need of more effective therapies. Increasing brain resilience may represent a new treatment strategy. Klotho, a longevity factor, enhances cognition when genetically and broadly overexpressed in its full, wild-type form over the mouse lifespan. Whether acute klotho treatment can rapidly enhance cognitive and motor functions or induce resilience is a gap in our knowledge of its therapeutic potential...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28782587/prolonged-ketamine-exposure-induces-increased-activity-of-the-glun2b-containing-n-methyl-d-aspartate-receptor-in-the-anterior-cingulate-cortex-of-neonatal-rats
#18
Saurabh S Kokane, Kerui Gong, Jianhui Jin, Qing Lin
Ketamine is a commonly used anesthetic among pediatric patients due to its high efficacy. However, it has been demonstrated by several preclinical studies that, widespread accelerated programmed death of neurons (neuroapoptosis) occurs due to prolonged or repeated exposure to ketamine specifically in the neonatal brain. Therefore, an emphasis on understanding the molecular mechanisms underlying this selective vulnerability of the neonatal brain to ketamine-induced neuroapoptosis becomes important in order to identify potential therapeutic targets, which would help prevent or at least ameliorate this neuroapoptosis...
August 4, 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/28761381/nmda-receptors-are-important-regulators-of-pancreatic-cancer-and-are-potential-targets-for-treatment
#19
William G North, Fuli Liu, Liz Z Lin, Ruiyang Tian, Bonnie Akerman
Pancreatic cancer, particularly adenocarcinoma of the pancreas, is a common disease with a poor prognosis. In this study, the importance of N-methyl-D-aspartate (NMDA) receptors for the growth and survival of pancreatic cancer was investigated. Immunohistochemistry performed with antibodies against GluN1 and GluN2B revealed that all invasive adenocarcinoma and neuroendocrine pancreatic tumors likely express these two NMDA receptor proteins. These proteins were found to be membrane components of pancreatic cancer cell lines, and both channel-blocker antagonist and GluN2B antagonist significantly reduced cell viability in vitro...
2017: Clinical Pharmacology: Advances and Applications
https://www.readbyqxmd.com/read/28760974/structural-basis-of-subunit-selectivity-for-competitive-nmda-receptor-antagonists-with-preference-for-glun2a-over-glun2b-subunits
#20
Genevieve E Lind, Tung-Chung Mou, Lucia Tamborini, Martin G Pomper, Carlo De Micheli, Paola Conti, Andrea Pinto, Kasper B Hansen
NMDA-type glutamate receptors are ligand-gated ion channels that contribute to excitatory neurotransmission in the central nervous system (CNS). Most NMDA receptors comprise two glycine-binding GluN1 and two glutamate-binding GluN2 subunits (GluN2A-D). We describe highly potent (S)-5-[(R)-2-amino-2-carboxyethyl]-4,5-dihydro-1H-pyrazole-3-carboxylic acid (ACEPC) competitive GluN2 antagonists, of which ST3 has a binding affinity of 52 nM at GluN1/2A and 782 nM at GluN1/2B receptors. This 15-fold preference of ST3 for GluN1/2A over GluN1/2B is improved compared with NVP-AAM077, a widely used GluN2A-selective antagonist, which we show has 11-fold preference for GluN1/2A over GluN1/2B...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
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