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https://www.readbyqxmd.com/read/27906494/alcohol-dependent-molecular-adaptations-of-the-nmda-receptor-system
#1
REVIEW
Nadege Morisot, Dorit Ron
Phenotypes such as motivation to consume alcohol, goal-directed alcohol seeking and habit formation contribute to the mechanisms underlying heavy alcohol use. Learning and memory processes greatly contribute to the establishment and maintenance of these behavioral phenotypes. The N-Methyl-D-Aspartate receptor (NMDAR) is a driving force of synaptic plasticity, a key cellular hallmark of learning and memory. Here, we describe data in rodents and humans linking signaling molecules that center around the NMDARs and behaviors associated with the development and/or maintenance of alcohol abuse...
December 1, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27899309/repeated-misdiagnosis-of-a-relapsed-atypical-anti-nmda-receptor-encephalitis-without-an-associated-ovarian-teratoma
#2
Weihe Zhang, Li Yan, Jinsong Jiao
We present an atypical case of relapsed anti-NMDAR encephalitis in a young female patient without an associated ovarian teratoma. She presented with recurrent seizure attacks with muscle weakness, psychosis, dyskinesia, autonomic failure and insomnia. She was first misdiagnosed as mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) then Hashimoto's encephalopathy due to diffuse cerebral lesions, elevated serum lactic acid concentration, increased amount of thyroid peroxidase and thyroglobulin antibodies in serum and diffuse lesions of the thyroid gland...
November 26, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27895553/glypican-6-enhances-n-methyl-d-aspartate-receptor-function-in-human-induced-pluripotent-stem-cell-derived-neurons
#3
Kaoru Sato, Kanako Takahashi, Yukari Shigemoto-Mogami, Kaori Chujo, Yuko Sekino
The in vitro use of neurons that are differentiated from human induced pluripotent stem cells (hiPSC-neurons) is expected to improve the prediction accuracy of preclinical tests for both screening and safety assessments in drug development. To achieve this goal, hiPSC neurons are required to differentiate into functional neurons that form excitatory networks and stably express N-methyl-D-aspartate receptors (NMDARs). Recent studies have identified some astrocyte-derived factors that are important for the functional maturation of neurons...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27889488/enhanced-ltp-in-aged-rats-detrimental-or-compensatory
#4
Júlia Pinho, Ruben Vale, Vânia L Batalha, Ana Rita Costenla, Raquel Dias, Diogo Rombo, Ana M Sebastião, Alexandre de Mendonça, Maria José Diógenes
Age-dependent memory deterioration has been well documented and yet an increase in rat hippocampal LTP upon aging has been reported. This poses the question of whether the enhanced LTP is a cause or an attempt to compensate the memory deficits described in aged rats. Hippocampal slices from young, adult and aged Wistar rats were pre-incubated, with an NMDA receptor (NMDAR) antagonist, memantine (1 μM, 4 h), and hippocampal LTP was evaluated. The results show that memantine significantly decreases the larger LTP magnitude recorded in hippocampal slices from aged rats without compromising LTP recorded in slices from young and adult animals...
November 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27880078/serine-racemase-is-expressed-in-islets-and-contributes-to-the-regulation-of-glucose-homeostasis
#5
Amber D Lockridge, Daniel C Baumann, Brian Akhaphong, Alleah Abrenica, Robert F Miller, Emilyn U Alejandro
NMDA receptors (NMDARs) have recently been discovered as functional regulators of pancreatic β-cell insulin secretion. While these excitatory receptor channels have been extensively studied in the brain for their role in synaptic plasticity and development, little is known about how they work in β-cells. In neuronal cells, NMDAR activation requires the simultaneous binding of glutamate and a rate-limiting co-agonist, such as D-serine. D-serine levels and availability in most of the brain rely on endogenous synthesis by the enzyme serine racemase (Srr)...
November 23, 2016: Islets
https://www.readbyqxmd.com/read/27879199/an-nmda-receptor-dependent-mechanism-for-subcellular-segregation-of-sensory-inputs-in-the-tadpole-optic-tectum
#6
Ali S Hamodi, Zhenyu Liu, Kara G Pratt
In the vertebrate CNS, afferent sensory inputs are targeted to specific depths or layers of their target neuropil. This patterning exists ab initio, from the very beginning, and therefore has been considered an activity-independent process. However, here we report that, during circuit development, the subcellular segregation of the visual and mechanosensory inputs to specific regions of tectal neuron dendrites in the tadpole optic tectum requires NMDA receptor activity. Blocking NMDARs during the formation of these sensory circuits, or removing the visual set of inputs, leads to less defined segregation, and suggests a correlation-based mechanism in which correlated inputs wire to common regions of dendrites...
November 23, 2016: ELife
https://www.readbyqxmd.com/read/27874976/etidronate-rescues-cognitive-deficits-through-improving-synaptic-transmission-and-suppressing-apoptosis-in-2-vessel-occlusion-model-rats
#7
Wen Li, Huijuan Yuan, Yao Yu, Yuen-Ki Cheong, Guogang Ren, Zhuo Yang
Vascular dementia (VD) is a neurodegenerative disorder caused by the reduction of cerebral blood flow. It shows a progressive cognitive impairment. In our previous study, we found that etidronate (ET) showed neuroprotective effects against glutamate-injured PC12 cells. Thus in this study, we aimed to observe the effects of ET on learning and memory impairment and the related mechanism in 2-vessel occlusion (2VO) model rats. Rats were administered a permanent bilateral common carotid artery occlusion to induce VD model...
November 22, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27872582/separate-ionotropic-and-metabotropic-glutamate-receptor-functions-in-depotentiation-vs-ltp-a-distinct-role-for-group1-mglur-subtypes-and-nmdars
#8
Amira Latif-Hernandez, Enrico Faldini, Tariq Ahmed, Detlef Balschun
Depotentiation (DP) is a mechanism by which synapses that have recently undergone long-term potentiation (LTP) can reverse their synaptic strengthening within a short time-window after LTP induction. Group 1 metabotropic glutamate receptors (mGluRs) were shown to be involved in different forms of LTP and long-term depression (LTD), but little is known about their roles in DP. Here, we generated DP by applying low-frequency stimulation (LFS) at 5 Hz after LTP had been induced by a single train of theta-burst-stimulation (TBS)...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27872179/anti-n-methyl-d-aspartate-nmda-receptor-encephalitis-a-survey-of-treatment-progress-and-prospects-from-pediatric-neurologists
#9
Ilana Kahn, Guy Helman, Adeline Vanderver, Elizabeth Wells
Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis has been shown to be a treatable form of autoimmune encephalitis, but there remains no standardized approach to immunotherapy. We designed an anonymous survey sent to members of the Child Neurology Society to identify the current practices among child neurologists. A total of 151 pediatric neurologists responded to the survey. With these responses we were able to highlight areas of practice uniformity, including first-line treatment with intravenous immunoglobulin and intravenous methylprednisone and initiation of disease-modifying therapy with rituximab alone...
November 21, 2016: Journal of Child Neurology
https://www.readbyqxmd.com/read/27871866/effects-of-the-glun2b-nmda-receptor-antagonist-ro-25-6981-on-two-types-of-behavioral-flexibility-in-rats
#10
Emma Clark, Kristen Antoniak, Alyssandra Feniquito, Hans C Dringenberg
Recent evidence has implicated N-methyl-d-aspartate receptors (NMDARs) in several aspects of learning and behavioral flexibility in rodents. Here, we examined the effects of treatment with Ro 25-6981, a selective antagonist of NMDARs containing GluN2B subunits, on two types of behavioral flexibility in rats, spatial reversal learning and set-shifting (spatial vs. motor strategy). To examine spatial reversal learning, rats were trained to swim to a hidden platform in a water maze over four days. On the following day, the platform was moved to a new location in the maze...
November 18, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27866902/the-atypical-antipsychotic-olanzapine-disturbs-depotentiation-by-modulating-machrs-and-impairs-reversal-learning
#11
Woo Seok Song, Jin Hee Cha, Sang Ho Yoon, Young Seon Cho, Kyeong-Yeol Park, Myoung-Hwan Kim
Antipsychotic medication is an essential component for treating schizophrenia, which is a serious mental disorder that affects approximately 1% of the global population. Olanzapine (Olz), one of the most frequently prescribed atypical antipsychotics, is generally considered a first-line drug for treating schizophrenia. In contrast to psychotic symptoms, the effects of Olz on cognitive symptoms of schizophrenia are still unclear. In addition, the mechanisms by which Olz affects the neural circuits associated with cognitive function are unknown...
November 17, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27865768/regulation-of-extrasynaptic-signaling-by-polysialylated-ncam-impact-for-synaptic-plasticity-and-cognitive-functions
#12
REVIEW
Hristo Varbanov, Alexander Dityatev
The activation of synaptic N-methyl-d-aspartate-receptors (NMDARs) is crucial for induction of synaptic plasticity and supports cell survival, whereas activation of extrasynaptic NMDARs inhibits long-term potentiation and triggers neurodegeneration. A soluble polysialylated form of the neural cell adhesion molecule (polySia-NCAM) suppresses signaling through peri-/extrasynaptic GluN2B-containing NMDARs. Genetic or enzymatic manipulations blocking this mechanism result in impaired synaptic plasticity and learning, which could be repaired by reintroduction of polySia, or inhibition of either GluN1/GluN2B receptors or downstream signaling through RasGRF1 and p38 MAP kinase...
November 16, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27862359/the-conversion-of-glutamate-by-glutamine-synthase-in-neocortical-astrocytes-from-juvenile-rat-is-important-to-limit-glutamate-spillover-and-peri-extrasynaptic-activation-of-nmda-receptors
#13
Yosra Trabelsi, Mohamed Amri, Hélène Becq, Florence Molinari, Laurent Aniksztejn
Glutamate transporters (EAATs) are important to maintain spatial and temporal specificity of synaptic transmission. Their efficiency to uptake and transport glutamate into the intracellular space depends on several parameters including the intracellular concentrations of Na(+) and glutamate, the elevations of which may slow down the cycling rate of EAATs. In astrocytes, glutamate is maintained at low concentration due to the presence of specific enzymes such as glutamine synthase (GS). GS inhibition results in cytosolic accumulation of glutamate suggesting that the conversion of glutamate by GS is important for EAATs operation...
November 12, 2016: Glia
https://www.readbyqxmd.com/read/27859797/in-vitro-and-in-vivo-effects-of-a-novel-dimeric-inhibitor-of-psd-95-on-excitotoxicity-and-functional-recovery-after-experimental-traumatic-brain-injury
#14
Jens Bak Sommer, Anders Bach, Hana Malá, Kristian Strømgaard, Jesper Mogensen, Darryl Scott Pickering
PSD-95 inhibitors have been shown to be neuroprotective in stroke, but have only to a very limited extent been evaluated in the treatment of traumatic brain injury (TBI) that has pathophysiological mechanisms in common with stroke. The aims of the current study were to assess the effects of a novel dimeric inhibitor of PSD-95, UCCB01-147, on histopathology and long-term cognitive outcome after controlled cortical impact (CCI) in rats. As excitotoxic cell death is thought to be a prominent part of the pathophysiology of TBI, we also investigated the neuroprotective effects of UCCB01-147 and related compounds on NMDA-induced cell death in cultured cortical neurons...
November 17, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27858086/interaction-between-nmda-and-cb2-function-in-the-dorsal-hippocampus-on-memory-consolidation-impairment-an-isobologram-analysis
#15
Mohammad Nasehi, Marziyeh Hajikhani, Mohaddeseh Ebrahimi-Ghiri, Mohammad-Reza Zarrindast
RATIONALE: Convincing evidence has supported the pivotal role of N-methyl-D-aspartate receptors (NMDARs) and CB2Rs in the regulation of learning and memory. OBJECTIVE: In this study, the role of hippocampal (CA1 region) CB2 receptors on aversive memory consolidation deficit induced by D-AP5, a NMDA receptor antagonist, was evaluated. METHODS: Adult male Wistar rats received cannula implants that bilaterally targeted the CA1 region. Long-term memory was examined using the step-through type of passive avoidance task...
November 17, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27857196/step-activation-by-g%C3%AE-q-coupled-gpcrs-opposes-src-regulation-of-nmda-receptors-containing-the-glun2a-subunit
#16
Meng Tian, Jian Xu, Gang Lei, Paul J Lombroso, Michael F Jackson, John F MacDonald
N-methyl-D-aspartate receptors (NMDARs) are necessary for the induction of synaptic plasticity and for the consolidation of learning and memory. NMDAR function is tightly regulated by functionally opposed families of kinases and phosphatases. Herein we show that the striatal-enriched protein tyrosine phosphatase (STEP) is recruited by Gαq-coupled receptors, including the M1 muscarinic acetylcholine receptor (M1R), and opposes the Src tyrosine kinase-mediated increase in the function of NMDARs composed of GluN2A...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27856084/difluorocyclobutylacetylenes-as-positive-allosteric-modulators-of-mglur5-with-reduced-bioactivation-potential
#17
Andrew P Degnan, Darrell Maxwell, Anand Balakrishnan, Jeffrey M Brown, Amy Easton, Michael Gulianello, Umesh Hanumegowda, Melissa Hill-Drzewi, Regina Miller, Kenneth S Santone, Arun Senapati, Eric E Shields, Digavalli V Sivarao, Ryan Westphal, Valerie J Whiterock, Xiaoliang Zhuo, Joanne J Bronson, John E Macor
Schizophrenia is a serious illness that affects millions of patients and has been associated with N-methyl-d-aspartate receptor (NMDAR) hypofunction. It has been demonstrated that activation of metabotropic glutamate receptor 5 (mGluR5) enhances NMDA receptor function, suggesting the potential utility of mGluR5 positive allosteric modulators (PAMs) in the treatment of schizophrenia. Herein we describe the optimization of an mGluR5 PAM by replacement of a phenyl with aliphatic heterocycles and carbocycles as a strategy to reduce bioactivation in a biaryl acetylene chemotype...
December 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27854088/long-term-and-strong-immunotherapy-to-treat-anti-n-methyl-d-aspartate-receptor-encephalitis-with-refractory-status-epilepticus
#18
Lan-Hsin Lee, Chien-Jung Lu
BACKGROUND: Anti-N-Methyl-D-Aspartate receptor (anti-NMDAR) encephalitis is responsive to immunotherapy and removal of tumor, but there is no consensus in the treatment of severe anti- NMDAR encephalitis with prolonged refractory status epilepticus (SE). CASE REPORT: A 17-year-old girl presented as acute psychosis, refractory seizures, hyperkinesia, autonomic instability, and soon progressed to a dissociative state of coma. Anti-NMDAR antibodies were positive in serum and CSF...
September 15, 2016: Acta Neurologica Taiwanica
https://www.readbyqxmd.com/read/27852777/amyloid-%C3%AE-peptide-nitrotyrosination-stabilizes-oligomers-and-enhances-nmdar-mediated-toxicity
#19
Biuse Guivernau, Jaume Bonet, Victòria Valls-Comamala, Mònica Bosch-Morató, Juan A Godoy, Nibaldo C Inestrosa, Alex Perálvarez-Marín, Xavier Fernández-Busquets, David Andreu, Baldomero Oliva, Francisco J Muñoz
: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the pathological aggregation of the amyloid-β peptide (Aβ). Monomeric soluble Aβ can switch from helicoidal to β-sheet conformation, promoting its assembly into oligomers and subsequently to amyloid fibrils. Oligomers are highly toxic to neurons and have been reported to induce synaptic transmission impairments. The progression from oligomers to fibrils forming senile plaques is currently considered a protective mechanism to avoid the presence of the highly toxic oligomers...
November 16, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27847466/glun2a-subunit-containing-nmda-receptors-are-the-preferential-neuronal-targets-of-homocysteine
#20
Dmitry A Sibarov, Polina A Abushik, Rashid Giniatullin, Sergei M Antonov
Homocysteine (HCY) is an endogenous redox active amino acid, best known as contributor to various neurodegenerative disorders. Although it is known that HCY can activate NMDA receptors (NMDARs), the mechanisms of its action on receptors composed of different NMDA receptor subunits remains almost unknown. In this study, using imaging and patch clamp technique in cultured cortical neurons and heterologous expression in HEK293T cells we tested the agonist activity of HCY on NMDARs composed of GluN1 and GluN2A subunits (GluN1/2A receptors) and GluN1 and GluN2B subunits (GluN1/2B receptors)...
2016: Frontiers in Cellular Neuroscience
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