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https://www.readbyqxmd.com/read/28214577/parafascicular-thalamic-nucleus-deep-brain-stimulation-decreases-nmda-receptor-glun1-subunit-gene-expression-in-the-prefrontal-cortex
#1
Mónica R Fernández-Cabrera, Abraham Selvas, Miguel Miguéns, Alejandro Higuera-Matas, Anna Vale-Martínez, Emilio Ambrosio, Margarita Martí-Nicolovius, Gemma Guillazo-Blanch
The rodent parafascicular nucleus (PFn) or the centromedian-parafascicular complex of primates is a posterior intralaminar nucleus of the thalamus related to cortical activation and maintenance of states of consciousness underlying attention, learning and memory. Deep brain stimulation (DBS) of the PFn has been proved to restore arousal and consciousness in humans and to enhance performance in learning and memory tasks in rats. The primary expected effect of PFn DBS is to induce plastic changes in target neurons of brain areas associated with cognitive function...
February 15, 2017: Neuroscience
https://www.readbyqxmd.com/read/28213516/rapid-regulation-of-sialidase-activity-in-response-to-neural-activity-and-sialic-acid-removal-during-memory-processing-in-rat-hippocampus
#2
Akira Minami, Yuko Meguro, Sayaka Ishibashi, Ami Ishii, Mako Shiratori, Saki Sai, Yuuki Horii, Hirotaka Shimizu, Hokuto Fukumoto, Sumika Shinba, Risa Taguchi, Tadanobu Takahashi, Tadamune Otsubo, Kiyoshi Ikeda, Takashi Suzuki
Sialidase cleaves sialic acids on the extracellular cell surface as well as inside the cell, and is necessary for normal long-term potentiation (LTP) at MF-CA3 pyramidal cell synapses and for hippocampus-dependent spatial memory. Here, we investigated in detail the role of sialidase in memory processing. Sialidase activity measured with 4MU-Neu5Ac or X-Neu5Ac and FRV LB was increased by high K(+)-induced membrane depolarization. Sialidase activity was also increased by chemical LTP induction with forskolin and activation of BDNF signaling, non-NMDARs or NMDARs...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213064/juvenile-treatment-with-a-novel-mglur2-agonist-mglur3-antagonist-compound-ly395756-reverses-learning-deficits-and-cognitive-flexibility-impairments-in-adults-in-a-neurodevelopmental-model-of-schizophrenia
#3
Meng-Lin Li, Yelena Gulchina, Sarah A Monaco, Bo Xing, Brielle R Ferguson, Yan-Chun Li, Feng Li, Xi-Quan Hu, Wen-Jun Gao
Schizophrenia (SCZ) is a neurodevelopmental psychiatric disorder, in which cognitive function becomes disrupted at early stages of the disease. Although the mechanisms underlying cognitive impairments remain unclear, N-methyl-D-aspartate receptors (NMDAR) hypofunctioning in the prefrontal cortex (PFC) has been implicated. Moreover, cognitive symptoms in SCZ are usually unresponsive to treatment with current antipsychotics and by onset, disruption of the dopamine system, not NMDAR hypofunctioning, dominates the symptoms...
February 14, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28210722/synthesis-radio-synthesis-and-in-vitro-evaluation-of-terminally-fluorinated-derivatives-of-hu-210-and-hu-211-as-novel-candidate-pet-tracers
#4
Chiara Zanato, Alessia Pelagalli, Katie F M Marwick, Monica Piras, Sergio Dall'Angelo, Andrea Spinaci, Roger G Pertwee, David J A Wyllie, Giles E Hardingham, Matteo Zanda
We report the synthesis of terminally fluorinated HU-210 and HU-211 analogues (HU-210F and HU-211F, respectively) and their biological evaluation as ligands of cannabinoid receptors (CB1 and CB2) and N-methyl d-aspartate receptor (NMDAR). [(18)F]-labelled HU-210F was radiosynthesised from the bromo-substituted precursor. In vitro assays showed that both HU-210F and HU-211F retain the potent pharmacological profile of HU-210 and HU-211, suggesting that [(18)F]-radiolabelled HU-210F and HU-211F could have potential as PET tracers for in vivo imaging...
February 17, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28210211/app-as-a-protective-factor-in-acute-neuronal-insults
#5
REVIEW
Dimitri Hefter, Andreas Draguhn
Despite its key role in the molecular pathology of Alzheimer's disease (AD), the physiological function of amyloid precursor protein (APP) is unknown. Increasing evidence, however, points towards a neuroprotective role of this membrane protein in situations of metabolic stress. A key observation is the up-regulation of APP following acute (stroke, cardiac arrest) or chronic (cerebrovascular disease) hypoxic-ischemic conditions. While this mechanism may increase the risk or severity of AD, APP by itself or its soluble extracellular fragment APPsα can promote neuronal survival...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28209905/diagnostic-value-of-18-f-fdg-pet-ct-versus-mri-in-the-setting-of-antibody-specific-autoimmune-encephalitis
#6
Lilja B Solnes, Krystyna M Jones, Steven P Rowe, Puskar Pattanayak, Abhinav Nalluri, Arun Venkatesan, John C Probasco, Mehrbod Som Javadi
Introduction: Diagnosis of autoimmune encephalitis presents some challenges in the clinical setting due to varied clinical presentations and delay in obtaining antibody panel results. We examined the role of neuroimaging in the setting of autoimmune encephalitides comparing the utility (18)F-FDG PET/CT versus conventional brain imaging with MRI. Methods: A retrospective study was performed assessing the positivity rate of MRI versus (18)F-FDG PET/CT during the initial work-up of 23 patients proven to have antibody positive autoimmune encephalitis...
February 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28209776/distance-dependent-gradient-in-nmdar-driven-spine-calcium-signals-along-tapering-dendrites
#7
Alison S Walker, Guilherme Neves, Federico Grillo, Rachel E Jackson, Mark Rigby, Cian O'Donnell, Andrew S Lowe, Gema Vizcay-Barrena, Roland A Fleck, Juan Burrone
Neurons receive a multitude of synaptic inputs along their dendritic arbor, but how this highly heterogeneous population of synaptic compartments is spatially organized remains unclear. By measuring N-methyl-d-aspartic acid receptor (NMDAR)-driven calcium responses in single spines, we provide a spatial map of synaptic calcium signals along dendritic arbors of hippocampal neurons and relate this to measures of synapse structure. We find that quantal NMDAR calcium signals increase in amplitude as they approach a thinning dendritic tip end...
February 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28206646/acute-melamine-affects-spatial-memory-consolidation-via-inhibiting-hippocampal-nmdar-dependent-ltd-in-rats
#8
Lei An, Wei Sun
No abstract text is available yet for this article.
February 16, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28202703/investigations-in-gabaa-receptor-antibody-associated-encephalitis
#9
Marianna Spatola, Mar Petit-Pedrol, Mateus Mistieri Simabukuro, Thaís Armangue, Fernanda J Castro, Maria I Barcelo Artigues, Maria R Julià Benique, Leslie Benson, Mark Gorman, Ana Felipe, Ruben L Caparó Oblitas, Myrna R Rosenfeld, Francesc Graus, Josep Dalmau
OBJECTIVE: To report the clinical features, comorbidities, receptor subunit targets, and outcome in patients with anti-GABAA receptor (GABAAR) encephalitis. METHODS: Clinical study of 26 patients, including 17 new (April 2013-January 2016) and 9 previously reported patients. Antibodies to α1, β3, and γ2 subunits of the GABAAR were determined using reported techniques. RESULTS: Patients' median age was 40.5 years (interquartile range 48...
February 15, 2017: Neurology
https://www.readbyqxmd.com/read/28202572/differential-regulation-of-nmda-receptors-by-d-serine-and-glycine-in-mammalian-spinal-locomotor-networks
#10
David Acton, Gareth Brian Miles
Activation of N-methyl-D-aspartate receptors (NMDARs) requires the binding of a co-agonist, either D-serine or glycine, in addition to glutamate. Changes in occupancy of the co-agonist binding site are proposed to modulate neural networks including those controlling swimming in frog tadpoles. Here, we characterize regulation of the NMDAR co-agonist binding site in mammalian spinal locomotor networks. Blockade of NMDARs by D(-)-2-amino-5-phosphonopentanoic acid (D-APV) or 5,7-dichlorokynurenic acid reduced the frequency and amplitude of pharmacologically induced locomotor-related activity recorded from the ventral roots of spinal-cord preparations from neonatal mice...
February 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28202503/vitamin-d-and-depression-cellular-and-regulatory-mechanisms
#11
REVIEW
Michael J Berridge
Depression is caused by a change in neural activity resulting from an increase in glutamate that drives excitatory neurons and may be responsible for the decline in the activity and number of the GABAergic inhibitory neurons. This imbalance between the excitatory and inhibitory neurons may contribute to the onset of depression. At the cellular level there is an increase in the concentration of intracellular Ca(2+) within the inhibitory neurons that is driven by an increase in entry through the NMDA receptors (NMDARs) and through activation of the phosphoinositide signaling pathway that generates inositol trisphosphate (InsP3) that releases Ca(2+) from the internal stores...
April 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/28202296/psychosis-in-the-ed-a-case-of-nmda-receptor-antibody-encephalitis
#12
Joseph Fisher, Clifford Ellingson, Noah Tolby
Anti-N-methyl-d-aspartate antibody receptor (NMDAR) encephalitis is a newly recognized disease increasing in diagnostic frequency. A 27-year-old female presented with symptoms of oral dyskinesia, tachycardia, and altered mental status following a three-month history of depression, lethargy, catatonia, and auditory hallucinations. We utilized our facilities neurology and psychiatry consult services, performed a lumbar puncture (LP), and requested NMDAR antibody titers. Following admission the Anti-NMDAR antibody titer was elevated warranting treatment with intravenous immunoglobulin (IVIG), corticosteroids, and later rituximab...
February 6, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28198441/pdi-regulates-seizure-activity-via-nmda-receptor-redox-in-rats
#13
Ji Yang Kim, Ah-Rhem Ko, Hye-Won Hyun, Su-Ji Min, Ji-Eun Kim
Redox modulation of cysteine residues is one of the post-translational modifications of N-methyl-D-aspartate receptor (NMDAR). Protein disulfide isomerases (PDI), an endoplasmic reticulum (ER) chaperone, plays a crucial role in catalyzing disulfide bond formation, reduction, and isomerization. In the present study, we found that PDI bound to NMDAR in the normal hippocampus, and that this binding was increased in chronic epileptic rats. In vitro thiol reductase assay revealed that PDI increased the amount of thiols on full-length recombinant NR1 protein...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28192149/serum-uric-acid-and-anti-n-methyl-d-aspartate-receptor-encephalitis
#14
Yaqing Shu, Yuge Wang, Tingting Lu, Rui Li, Xiaobo Sun, Jing Li, Yanyu Chang, Xueqiang Hu, Zhengqi Lu, Wei Qiu
BACKGROUND: Uric acid (UA) levels are associated with autoimmune and neurodegenerative disorders, but their relationship with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is unknown. METHODS: UA levels were evaluated in 58 patients with anti-NMDAR encephalitis, and 58 age- and sex-matched healthy controls (CTLs). Follow-up evaluations of 30 out of the 58 patients with anti-NMDAR encephalitis were conducted 3 months after admission. Modified Rankin scale (mRS) scores and clinical and cerebrospinal fluid parameters were evaluated in all anti-NMDAR encephalitis patients...
February 9, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28192131/the-effects-of-low-dose-mk-801-administration-on-nmdar-dependent-executive-functions-in-pigeons
#15
Nurper Gökhan, Lorenz S Neuwirth, Edward F Meehan
No abstract text is available yet for this article.
February 10, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28190661/the-novel-antipsychotic-drug-brexpiprazole-alone-and-in-combination-with-escitalopram-facilitates-prefrontal-glutamatergic-transmission-via-a-dopamine-d1-receptor-dependent-mechanism
#16
Carl Björkholm, Monica M Marcus, Åsa Konradsson-Geuken, Kent Jardemark, Torgny H Svensson
Brexpiprazole (Rexulti(®)), a novel D2/3 receptor (R) partial agonist, was recently approved as monotherapy for schizophrenia, demonstrating effectiveness against both positive and negative symptoms, and also approved as add-on treatment to antidepressant drugs, inducing a potent antidepressant effect with a faster onset compared to an antidepressant given alone. Moreover, brexpiprazole has demonstrated pro-cognitive effects in preclinical studies. To explore whether the observed effects may be mediated via modulation of prefrontal glutamatergic transmission, we investigated the effect of brexpiprazole, alone and in combination with the SSRI escitalopram, on prefrontal glutamatergic transmission using in vitro electrophysiological intracellular recordings of deep layer pyramidal cells of the rat medial prefrontal cortex (mPFC)...
February 9, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28189671/global-sensitivity-analysis-of-a-model-related-to-memory-formation-in-synapses-model-reduction-based-on-epistemic-parameter-uncertainties-and-related-issues
#17
Don Kulasiri, Jingyi Liang, Yao He, Sandhya Samarasinghe
We investigate the epistemic uncertainties of parameters of a mathematical model that describes the dynamics of CaMKII-NMDAR complex related to memory formation in synapses using global sensitivity analysis (GSA). The model, which was published in this journal, is nonlinear and complex with Ca(2+) patterns with different level of frequencies as inputs. We explore the effects of parameter on the key outputs of the model to discover the most sensitive ones using GSA and partial ranking correlation coefficient (PRCC) and to understand why they are sensitive and others are not based on the biology of the problem...
February 9, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28187950/advancing-nmda-receptor-physiology-by-integrating-multiple-approaches
#18
REVIEW
Huan-Xiang Zhou, Lonnie P Wollmuth
NMDA receptors (NMDARs) are ion channels activated by the excitatory neurotransmitter glutamate and are essential to all aspects of brain function, including learning and memory formation. Missense mutations distributed throughout NMDAR subunits have been associated with an array of neurological disorders. Recent structural, functional, and computational studies have generated many insights into the activation process connecting glutamate binding to ion-channel opening, which is central to NMDAR physiology and pathophysiology...
February 7, 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/28186680/the-group-ii-metabotropic-glutamate-receptor-agonist-ly354740-and-the-d2-receptor-antagonist-haloperidol-reduce-locomotor-hyperactivity-but-fail-to-rescue-spatial-working-memory-in-glua1-knockout-mice
#19
Thomas Boerner, Alexei Bygrave, Jingkai Chen, Anushka Fernando, Stephanie Jackson, Chris Barkus, Rolf Sprengel, Peter H Seeburg, Paul J Harrison, Gary Gilmour, David M Bannerman, David J Sanderson
Group II metabotropic glutamate receptor agonists have been suggested as potential anti-psychotics, at least in part, based on the observation that the agonist LY354740 appeared to rescue the cognitive deficits caused by non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonists, including spatial working memory deficits in rodents. Here, we tested the ability of LY354740 to rescue spatial working memory performance in mice that lack the GluA1 subunit of the AMPA glutamate receptor, encoded by Gria1, a gene recently implicated in schizophrenia by genome-wide association studies...
February 10, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28186166/selective-molecular-impairment-of-spontaneous-neurotransmission-modulates-synaptic-efficacy
#20
Devon C Crawford, Denise M O Ramirez, Brent Trauterman, Lisa M Monteggia, Ege T Kavalali
Recent studies suggest that stimulus-evoked and spontaneous neurotransmitter release processes are mechanistically distinct. Here we targeted the non-canonical synaptic vesicle SNAREs Vps10p-tail-interactor-1a (vti1a) and vesicle-associated membrane protein 7 (VAMP7) to specifically inhibit spontaneous release events and probe whether these events signal independently of evoked release to the postsynaptic neuron. We found that loss of vti1a and VAMP7 impairs spontaneous high-frequency glutamate release and augments unitary event amplitudes by reducing postsynaptic eukaryotic elongation factor 2 kinase (eEF2K) activity subsequent to the reduction in N-methyl-D-aspartate receptor (NMDAR) activity...
February 10, 2017: Nature Communications
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