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https://www.readbyqxmd.com/read/29141213/cpeb2-activates-grasp1-mrna-translation-and-promotes-ampa-receptor-surface-expression-long-term-potentiation-and-memory
#1
Wen-Hsin Lu, Nai-Hsing Yeh, Yi-Shuian Huang
Activity-dependent synthesis of plasticity-related proteins is necessary to sustain long-lasting synaptic modifications and consolidate memory. We investigated the role of the translational regulator cytoplasmic polyadenylation element binding protein 2 (CPEB2) in learning and memory because regulated mRNA translation contributes to synaptic plasticity. Forebrain-restricted CPEB2 conditional knockout (cKO) mice exhibited impaired hippocampus-dependent memory in contextual fear conditioning and Morris water maze tests...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29123470/regulation-of-ampa-receptor-trafficking-by-protein-ubiquitination
#2
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/29118000/ca-2-calmodulin-binding-to-psd-95-mediates-homeostatic-synaptic-scaling-down
#3
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/29107806/chronic-hyperammonemia-alters-in-opposite-ways-membrane-expression-of-glua1-and-glua2-ampa-receptor-subunits-in-cerebellum-molecular-mechanisms-involved
#4
Andrea Cabrera-Pastor, Lucas Taoro-González, Esperanza López-Merino, Ferran Celma, Marta Llansola, Vicente Felipo
Hyperammonemia contributes to altered neurotransmission and cognition in patients with hepatic encephalopathy. Hyperammonemia in rats affects differently high- and low-affinity AMPA receptors (AMPARs) in cerebellum. We hypothesized that hyperammonemia would alter differently membrane expression of AMPARs GluA1 and GluA2 subunits by altering its phosphorylation. This work aims were: 1) assess if hyperammonemia alters GluA1 and GluA2 subunits membrane expression in cerebellum and 2) analyze the underlying mechanisms...
October 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29089441/glutamate-activates-ampa-receptor-conductance-in-the-developing-schwann-cells-of-the-mammalian-peripheral-nerves
#5
Ting-Jiun Chen, Nicole Fröhlich, Bartosz Kula, Ruxandra Barzan, Maria Kukley
Schwann cells (SCs) are myelinating cells of the peripheral nervous system. Although SCs are known to express different channels and receptors on their surface, little is known about the activation and function of these proteins. Ionotropic glutamate receptors are thought to play an essential role during development of SC lineage and during peripheral nerve injury and therefore we sought to study their functional properties. We established a novel preparation of living peripheral nerve slices with preserved cellular architecture, and used a patch-clamp technique to study α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic-acid (AMPA)-receptor-mediated currents in SCs for the first time...
October 31, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29075658/improving-the-antibody-based-evaluation-of-autoimmune-encephalitis
#6
Lindsey McCracken, Junxian Zhang, Maxwell Greene, Anne Crivaro, Joyce Gonzalez, Malek Kamoun, Eric Lancaster
OBJECTIVE: We tested whether antibody screening samples of patients with suspected autoimmune encephalitis with additional research assays would improve the detection of autoimmune encephalitis compared with standard clinical testing alone. METHODS: We examined 731 samples (333 CSF, 182 sera, and 108 pairs) from a cohort of 623 patients who were tested for CNS autoantibodies by the University of Pennsylvania clinical laboratory over a 24-month period with cell-based assays (CBAs) on commercially obtained slides of fixed cells for antibodies to NMDA receptor (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), γ-aminobutyric acid-B receptor (GABABR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (Caspr2), and glutamic acid decarboxylase (GAD65)...
November 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/29046349/differential-regulation-of-the-rac1-gtpase-activating-protein-gap-bcr-during-oxygen-glucose-deprivation-in-hippocampal-and-cortical-neurons
#7
Katharine R Smith, Dipen Rajgor, Jonathan G Hanley
Brain ischemia causes oxygen and glucose deprivation (OGD) in neurons, triggering a cascade of events leading to synaptic accumulation of glutamate. Excessive activation of glutamate receptors causes excitotoxicity and delayed cell death in vulnerable neurons. Following global cerebral ischemia, hippocampal CA1 pyramidal neurons are more vulnerable to injury than their cortical counterparts, but the mechanisms that underlie this difference are unclear. Signalling via Rho-family small GTPases, their upstream Guanine nucleotide Exchange Factors (GEFs) and GTPase Activating Proteins (GAPs) is differentially dysregulated in response to OGD/ischemia in hippocampal and cortical neurons...
October 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29042315/il-1%C3%AE-reduces-glua1-phosphorylation-and-its-surface-expression-during-memory-reconsolidation-and-%C3%AE-melanocyte-stimulating-hormone-can-modulate-these-effects
#8
Ivana Machado, Helgi B Schiöth, Mercedes Lasaga, Teresa Scimonelli
Pro-inflammatory cytokines can affect cognitive processes such as learning and memory. Particularly, interleukin-1β (IL-1β) influences hippocampus-dependent memories. We previously reported that administration of IL-1β in dorsal hippocampus impaired contextual fear memory reconsolidation. This effect was reversed by the melanocortin alpha-melanocyte-stimulating hormone (α-MSH). Our results also demonstrated that IL-1β produced a significant decrease in glutamate release from dorsal hippocampus synaptosomes after reactivation of the fear memory...
October 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29029785/a-single-dose-of-cocaine-potentiates-glutamatergic-synaptic-transmission-onto-locus-coeruleus-neurons
#9
Feipeng Zhu, Qihui Wu, Jie Li, Katarzyna Grycel, Bing Liu, Xiaoxuan Sun, Li Zhou, Ruiyin Jiao, Rui Song, Younus M Khan, Qinglong Wang, Lun Wang, Yongxin Xu, Jin Li, Bo Zhang, Zhuan Zhou
The brainstem locus coeruleus (LC), the primary norepinephrinergic (NE) nucleus in the brain, has been implicated in the abuse of drugs such as opioids. However, whether and how the LC-NE system is involved in cocaine addiction remains elusive. Here, we demonstrated cocaine-evoked synaptic plasticity of glutamatergic transmission onto LC neurons as one of the earliest traces occurring after a single injection of cocaine. Twenty-four hours after mice were injected intraperitoneally with cocaine, the evoked α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) mediated synaptic transmission onto LC neurons were strongly potentiated without major effect on N-methyl-d-aspartate receptor (NMDAR) mediated synaptic transmission...
November 2017: Cell Calcium
https://www.readbyqxmd.com/read/29019029/hippocampal-acetylation-may-improve-prenatal-stress-induced-depression-like-behavior-of-male-offspring-rats-through-regulating-ampars-expression
#10
Yong Lu, Junli Zhang, Lin Zhang, Shaokang Dang, Qian Su, Huiping Zhang, Tianwei Lin, Xiaoxiao Zhang, Yurong Zhang, Hongli Sun, Zhongliang Zhu, Hui Li
This study is to determine the role and mechanism of hippocampal acetylation in prenatal stress (PS) induced depression-like behavior of male offspring rats. PS-induced depression rat model was established. Sucrose preference and forced swim test were used to observe the behavior changes of male offspring rats. Hippocampal acetylation was induced by Trichostatin A injection. Quantitative real-time PCR and Western blot were used to determine the changes of AMPARs in acetylated hippocampus. The behavioral tests proved that AMPA was involved in the PS-induced depression-like behavior in offspring rats...
October 10, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29016847/a-point-mutation-in-the-ion-conduction-pore-of-ampa-receptor-gria3-causes-dramatically-perturbed-sleep-patterns-as-well-as-intellectual-disability
#11
Benjamin Davies, Laurence A Brown, Ondrej Cais, Jake Watson, Amber J Clayton, Veronica T Chang, Daniel Biggs, Christopher Preece, Polinka Hernandez-Pliego, Jon Krohn, Amarjit Bhomra, Stephen R F Twigg, Andrew Rimmer, Alexander Kanapin, Arjune Sen, Zenobia Zaiwalla, Gil McVean, Russell Foster, Peter Donnelly, Jenny C Taylor, Edward Blair, David Nutt, A Radu Aricescu, Ingo H Greger, Stuart N Peirson, Jonathan Flint, Hilary C Martin
The discovery of genetic variants influencing sleep patterns can shed light on the physiological processes underlying sleep. As part of a large clinical sequencing project, WGS500, we sequenced a family in which the two male children had severe developmental delay and a dramatically disturbed sleep-wake cycle, with very long wake and sleep durations, reaching up to 106-h awake and 48-h asleep. The most likely causal variant identified was a novel missense variant in the X-linked GRIA3 gene, which has been implicated in intellectual disability...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28988523/immunopathology-in-drug-resistant-mesial-temporal-lobe-epilepsy-with-different-types-of-hippocampal-sclerosis
#12
F Irsel Tezer, Aysegul Firat, Erdem Tuzun, Isik Unal, Figen Soylemezoglu, Burcak Bilginer, Figen Kaymaz, Kader K Oguz, Serap Saygi
PURPOSE: There is evidence that autoimmunity has a specific role in temporal lobe seizures of limbic encephalitis patients. Our aim in this study was to investigate any histopathological clues of autoimmune process in refractory temporal lobe epilepsy (TLE) patients with different pathologically proven hippocampal sclerosis (HS) types. METHODS: 22 patients who had undergone to epilepsy surgery due to mesial TLE-HS were included. The sera of patients are tested for neuronal antibodies to NMDAR, LGI1, CASPR2, AMPAR, GABABR and GAD...
October 7, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/28986876/electrophysiological-investigation-of-nmda-current-properties-in-brain-slices
#13
Alexandre Pons-Bennaceur, Natalia Lozovaya
Analysis of electrophysiological properties of NMDARs and NMDAR-mediated synaptic transmission in identified neurons and synapses in brain slices is a major step in understanding their function in normal and pathological neuronal brain networks. In many central synapses excitatory postsynaptic currents (EPSCs) are mediated by excitatory neurotransmitter glutamate that activates colocalized AMPAR and NMDAR generating a complex EPSC. Here, we describe the methods commonly used in brain slices to study the electrophysiological properties of NMDAR-mediated component of spontaneous or evoked EPSCs by extracellular stimulation or by stimulating synaptically connected neurons...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28975619/impaired-ampa-receptor-trafficking-by-a-double-knockout-of-zebrafish-olfactomedin1a-b
#14
Naoki Nakaya, Afia Sultana, Stanislav I Tomarev
The olfm1a and olfm1b genes in zebrafish encode conserved secreted glycoproteins. These genes are preferentially expressed in the brain and retina starting from 16 h post-fertilization until adulthood. Functions of the Olfm1 gene is still unclear. Here, we produced and analyzed a null zebrafish mutant of both olfm1a and olfm1b genes (olfm1 null). olfm1 null fish were born at a normal Mendelian ratio and showed normal body shape and fertility as well as no visible defects from larval stages to adult. Olfm1 proteins were preferentially localized in the synaptosomes of the adult brain...
October 4, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28973019/beta-arrestin-1-regulation-of-reward-motivated-behaviors-and-glutamatergic-function
#15
Nitish Mittal, Ani Minasyan, Nicole Romaneschi, Joshua K Hakimian, Gabriel Gonzalez-Fernandez, Ralph Albert, Nina Desai, Ian A Mendez, Timothy Schallert, Sean B Ostlund, Wendy Walwyn
The two highly homologous non-visual arrestins, beta-arrestin 1 and 2, are ubiquitously expressed in the central nervous system, yet knowledge of their disparate roles is limited. While beta-arrestin 2 (βarr2) has been implicated in several aspects of reward-related learning and behavior, very little is known about the behavioral function of beta-arrestin 1 (βarr1). Using mice lacking βarr1, we focused on the role of this scaffolding and signal transduction protein in reward-motivated behaviors and in striatal glutamatergic function...
2017: PloS One
https://www.readbyqxmd.com/read/28969983/roles-for-arc-in-metabotropic-glutamate-receptor-dependent-ltd-and-synapse-elimination-implications-in-health-and-disease
#16
REVIEW
Julia R Wilkerson, Joseph P Albanesi, Kimberly M Huber
The Arc gene is robustly transcribed in specific neural ensembles in response to experience-driven activity. Upon induction, Arc mRNA is transported to dendrites, where it can be rapidly and locally translated by activation of metabotropic glutamate receptors (mGluR1/5). mGluR-induced dendritic synthesis of Arc is implicated in weakening or elimination of excitatory synapses by triggering endocytosis of postsynaptic AMPARs in both hippocampal CA1 and cerebellar Purkinje neurons. Importantly, CA1 neurons with experience-induced Arc mRNA are susceptible, or primed for mGluR-induced long-term synaptic depression (mGluR-LTD)...
October 13, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28968657/pharmacological-modulation-of-ampar-rescues-intellectual-disability-like-phenotype-in-tm4sf2-y-mice
#17
Luca Murru, Elena Vezzoli, Anna Longatti, Luisa Ponzoni, Andrea Falqui, Alessandra Folci, Edoardo Moretto, Veronica Bianchi, Daniela Braida, Mariaelvina Sala, Patrizia D'Adamo, Silvia Bassani, Maura Francolini, Maria Passafaro
Intellectual disability affects 2-3% of the world's population and typically begins during childhood, causing impairments in social skills and cognitive abilities. Mutations in the TM4SF2 gene, which encodes the TSPAN7 protein, cause a severe form of intellectual disability, and currently, no therapy is able to ameliorate this cognitive impairment. We previously reported that, in cultured neurons, shRNA-mediated down-regulation of TSPAN7 affects AMPAR trafficking by enhancing PICK1-GluA2 interaction, thereby increasing the intracellular retention of AMPAR...
August 31, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28965835/dopamine-induces-glutamate-accumulation-in-astrocytes-to-disrupt-neuronal-function-leading-to-pathogenesis-of-minimal-hepatic-encephalopathy
#18
Saidan Ding, Xuebao Wang, Weishan Zhuge, Jianjing Yang, Qichuan Zhuge
Minimal hepatic encephalopathy (MHE) is induced by elevated intracranial dopamine (DA). Glutamate (Glu) toxicity is known to be involved in many neurological disorders. In this study, we investigated whether DA increased Glu levels and collaborated with Glu to impair memory. We found that DA upregulated TAAR1, leading to reduced EAAT2 expression and Glu clearance in primary cortical astrocytes (PCAs). High DA increased TAAR1 expression, and high Glu increased AMPAR expression, inducing the activation of CaN/NFAT signaling and a decrease in the production of BDNF (Brain Derived Nerve Growth Factor)/NT3 (neurotrophin-3) in primary cortical neurons (PCNs)...
December 4, 2017: Neuroscience
https://www.readbyqxmd.com/read/28954337/-clinical-analysis-of-paraneoplastic-neurological-syndrome-associated-with-thymoma
#19
H S Liu, H T Ren, L X Zhou, S Q Li, B Peng, L Y Cui, H Z Guan
Objectives: To investigate the clinical features, diagnosis and treatment of antibody mediated paraneoplastic neurological syndrome associated with thymoma. Methods: From 2012 to 2017, the paraneoplastic antibody and neuron antibody were tested from both blood and cerebrospinal fluid (CSF) in consecutive patients clinically suspected with neurological paraneoplastic syndromes/unknown encephalitis in Peking Union Medical College Hospital.The clinical data, lab results, electrophysiological examinations, imaging features, treatment and clinical prognosis were collected...
September 19, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28951554/endocytosis-and-lysosomal-degradation-of-glua2-3-ampars-in-response-to-oxygen-glucose-deprivation-in-hippocampal-but-not-cortical-neurons
#20
Zsombor Koszegi, Maria Fiuza, Jonathan G Hanley
Global cerebral ischemia results in oxygen and glucose deprivation (OGD) and consequent delayed cell death of vulnerable neurons, with hippocampal CA1 neurons more vulnerable than cortical neurons. Most AMPA receptors (AMPARs) are heteromeric complexes of subunits GluA1/GluA2 or GluA2/GluA3, and the presence of GluA2 renders AMPARs Ca(2+)-impermeable. In hippocampal CA1 neurons, OGD causes the synaptic expression of GluA2-lacking Ca(2+)-permeable AMPARs, contributing to toxic Ca(2+) influx. The loss of synaptic GluA2 is caused by rapid trafficking of GluA2-containing AMPARs from the cell surface, followed by a delayed reduction in GluA2 mRNA expression...
September 26, 2017: Scientific Reports
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