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https://www.readbyqxmd.com/read/29346767/functional-principles-of-posterior-septal-inputs-to-the-medial-habenula
#1
Yo Otsu, Salvatore Lecca, Katarzyna Pietrajtis, Charly Vincent Rousseau, Païkan Marcaggi, Guillaume Pierre Dugué, Caroline Mailhes-Hamon, Manuel Mameli, Marco Alberto Diana
The medial habenula (MHb) is an epithalamic hub contributing to expression and extinction of aversive states by bridging forebrain areas and midbrain monoaminergic centers. Although contradictory information exists regarding their synaptic properties, the physiology of the excitatory inputs to the MHb from the posterior septum remains elusive. Here, combining optogenetics-based mapping with ex vivo and in vivo physiology, we examine the synaptic properties of posterior septal afferents to the MHb and how they influence behavior...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29339791/the-glun2a-subunit-regulates-neuronal-nmda-receptor-induced-microglia-neuron-physical-interactions
#2
Ukpong B Eyo, Ashley Bispo, Junting Liu, Sruchika Sabu, Rong Wu, Victoria L DiBona, Jiaying Zheng, Madhuvika Murugan, Huaye Zhang, Yamei Tang, Long-Jun Wu
Microglia are known to engage in physical interactions with neurons. However, our understanding of the detailed mechanistic regulation of microglia-neuron interactions is incomplete. Here, using high resolution two photon imaging, we investigated the regulation of NMDA receptor-induced microglia-neuron physical interactions. We found that the GluN2A inhibitor NVPAAM007, but not the GluN2B inhibitor ifenprodil, blocked the occurrence of these interactions. Consistent with the well-known developmental regulation of the GluN2A subunit, these interactions are absent in neonatal tissues...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339324/oscillatory-synchronous-inhibition-in-the-basolateral-amygdala-and-its-primary-dependence-on-nr2a-containing-nmda-receptors
#3
Vassiliki Aroniadou-Anderjaska, Volodymyr I Pidoplichko, Taiza H Figueiredo, Maria F M Braga
Synchronous, rhythmic firing of GABAergic interneurons is a fundamental mechanism underlying the generation of brain oscillations, and evidence suggests that NMDA receptors (NMDARs) play a key role in oscillatory activity by regulating the activity of interneurons. Consistent with this, derangement of brain rhythms in certain neuropsychiatric disorders, notably schizophrenia and autism, is associated with NMDAR hypofunction and loss of inhibitory interneurons. In the basolateral amygdala (BLA)-dysfunction of which is involved in a host of neuropsychiatric diseases-, principal neurons display spontaneous, rhythmic "bursts" of inhibitory activity, which could potentially be involved in the orchestration of oscillations in the BLA network; here, we investigated the role of NMDARs in these inhibitory oscillations...
January 12, 2018: Neuroscience
https://www.readbyqxmd.com/read/29335819/nmda-receptor-glun2-subtypes-control-epileptiform-events-in-the-hippocampus
#4
Pradeep Punnakkal, Deity Dominic
NMDA receptors (NMDARs) play a key role in synaptic plasticity and excitotoxicity. Subtype-specific role of NMDAR in neural disorders is an emerging area. Recent studies have revealed that mutations in NMDARs are a cause for epilepsy. Hippocampus is a known focal point for epilepsy. In hippocampus, expression of the NMDAR subtypes GluN1/GluN2A and GluN1/GluN2B is temporally regulated. However, the pharmacological significance of these subtypes is not well understood in epileptic context/models. To investigate this, epilepsy was induced in hippocampal slices by the application of artificial cerebrospinal fluid that contained high potassium but no magnesium...
January 15, 2018: Neuromolecular Medicine
https://www.readbyqxmd.com/read/29307084/glun2b-subunit-of-the-nmda-receptor-the-keystone-of-the-effects-of-alcohol-during-neurodevelopment
#5
Mickaël Naassila, Olivier Pierrefiche
The glutamatergic system plays a central role in both the acute and chronic effects of ethanol. Among all the glutamate receptors the ionotropic NMDA receptors are crucial because of their role in synaptic plasticity. A large body of evidences suggests that short-term and long-term effects of ethanol may change synaptic plasticity via an alteration of the expression of the GluN2B subunit, one constitutive element of the NMDA receptor. The present review is focusing on the role of the GluN2B subunit after ethanol exposure during early life (in utero and adolescence) and also at adulthood...
January 6, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29285738/developmental-changes-of-synaptic-and-extrasynaptic-nmda-receptor-expression-in-rat-cerebellar-neurons-in-vitro
#6
Dmitry A Sibarov, Yulia D Stepanenko, Ivan V Silantiev, Polina A Abushik, Tatiana V Karelina, Sergei M Antonov
Transient expression of different NMDA receptors (NMDARs) plays a role in development of the cerebellum. Whether similar processes undergo during neuronal differentiation in culture is not clearly understood. We studied NMDARs in cerebellar neurons in cultures of 7 and 21 days in vitro (DIV) using immunocytochemical and electrophysiological approaches. Whereas at 7 DIV, the vast majority of neurons were immunopositive for GluN2 subunits, further synaptoginesis was accompanied by the time-dependent loss of NMDARs...
December 28, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29242355/the-bioactive-protein-ligand-conformation-of-glun2c-selective-positive-allosteric-modulators-bound-to-the-nmda-receptor
#7
Thomas Maxwell Kaiser, Steven A Kell, Hirofumi Kusumoto, Gil Shaulsky, Subhrajit Bhattacharya, Matthew P Epplin, Katie L Strong, Eric J Miller, Bryan D Cox, David S Menaldino, Dennis C Liotta, Stephen F Traynelis, Pieter Buys Burger
NMDA receptors are ligand-gated, cation-selective channels that mediate a slow component of excitatory synaptic transmission. Subunit-selective positive allosteric modulators of NMDA receptor function have therapeutically-relevant effects on multiple processes in the brain. A series of pyrrolidinones, such as PYD-106, that selectively potentiate NMDA receptors that contain the GluN2C subunit have structural determinants of activity that reside between the GluN2C amino terminal domain and the GluN2C agonist binding domain, suggesting a unique site of action...
December 14, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29242136/anxiolytic-effect-of-cpeb1-knockdown-on-the-amygdala-of-a-mouse-model-of-inflammatory-pain
#8
Jiao Yue, Xin-Shang Wang, Yan-Yan Guo, Kai-Yin Zheng, Hai-Yan Liu, Li-Ning Hu, Ming-Gao Zhao, Shui-Bing Liu
Anxiety disorders are a category of mental disorders characterized by feelings of anxiety, stress, and fear attached to various sources. However, their pathogenesis is complicated and has not been fully elucidated. The amygdala is a vital brain region that regulates anxiety and mental disorders. Cytoplasmic polyadenylation element binding protein 1 (CPEB1) mediates the extension of the mRNA polyadenylation tail and facilitates the translation of target RNA. CPEB1 is closely related to neuronal diseases, such as Fragile X Syndrome, learning and memory disorders, and chronic pain...
December 11, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29176858/sepsis-induced-selective-loss-of-nmda-receptors-modulates-hippocampal-neuropathology-in-surviving-septic-mice
#9
Shuibing Zhang, Xueqin Wang, Sha Ai, Wen Ouyang, Yuan Le, Jianbin Tong
BACKGROUND: Sepsis-induced neuroinflammation plays an important role in sepsis-related brain dysfunction. However, the molecules that are targeted during neuroinflammation resulting from sepsis-induced brain dysfunction remain unclear. Herein, we tried to investigate the expression and roles of NMDA receptor subunits during sepsis-related brain dysfunction. METHODS: Sepsis was induced by cecal ligation and perforation (CLP) or by a single intraperitoneal injection of lipopolysaccharide (LPS, 8 mg/kg) in C57BL/6J mice...
2017: PloS One
https://www.readbyqxmd.com/read/29173480/changed-expressions-of-n-methyl-d-aspartate-receptors-in-the-brains-of-rats-and-primary-neurons-exposed-to-high-level-of-fluoride
#10
Na Wei, Yang-Ting Dong, Jie Deng, Ya Wang, Xiao-Lan Qi, Wen-Feng Yu, Yan Xiao, Jian-Jiang Zhou, Zhi-Zhong Guan
Expressions of N-methyl-d-aspartic acid receptors (NMDARs) in the brains of rats and primary neurons exposed to high fluoride were investigated. Sprague-Dawley rats were divided randomly into a fluorosis group (50ppm fluoride in the drinking water for 6 months) and controls (<0.5ppm fluoride) and the offspring from these rats sacrificed on postnatal days 1, 7, 14, 21 and 28. The primary cultured neurons from the hippocampus of neonatal rats were treated with 5 and 50ppm fluoride for 48h. NMDAR subunits at protein or mRNA levels were quantified by Western blotting or real-time PCR...
January 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29146480/neuroprotection-by-chotosan-a-kampo-formula-against-glutamate-excitotoxicity-involves-the-inhibition-of-glun2b-but-not-glun2a-containing-nmda-receptor-mediated-responses-in-primary-cultured-cortical-neurons
#11
Sachie Sasaki-Hamada, Azusa Suzuki, Emi Sanai, Kinzo Matsumoto, Jun-Ichiro Oka
Chotosan (CTS), a traditional herbal formula called Kampo medicine, was shown to be effective in the treatment of vascular dementia in a clinical study, and exerted protective effects against transient cerebral ischemia-induced cognitive impairment in mice. In the present study, we investigated the neuroprotective effects of CTS using primary cultured rat cortical neurons. CTS (250-1000 μg/mL) inhibited neuronal death induced by 100 μM glutamate. This glutamate-induced neuronal death was blocked by a GluN2B-, but not GluN2A-containing NMDA receptor antagonist...
November 1, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29127002/post-acquisition-hippocampal-blockade-of-the-nmda-receptor-subunit-glun2a-but-not-glun2b-sustains-spatial-reference-memory-retention
#12
Keisuke Shinohara, Toshimichi Hata
While it has been shown that the blockade of N-methyl-d-aspartate type glutamate receptors (NMDARs) impairs memory acquisition, recent studies have reported that the post-acquisition administration of NMDAR antagonists suppresses spatial memory decay. These findings suggest that NMDARs are important not only for the acquisition of new memories but also for the decay of previously acquired memories. The present study investigated the contributions of specific NMDAR subunits to spatial memory decay using NVP-AAM077 (NVP), an NMDAR antagonist that preferentially binds to GluN2A subunits, and the selective GluN2B blocker Ro 25-6981 (Ro)...
November 7, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29101031/a-deficiency-of-the-glun2c-subunit-of-the-n-methyl-d-aspartate-receptor-is-neuroprotective-in-a-mouse-model-of-ischemic-stroke
#13
Adam Holmes, Ning Zhou, Deborah L Donahue, Rashna Balsara, Francis J Castellino
The N-methyl-d-aspartate receptor (NMDAR) ion channel plays a pivotal role in the pathology of ischemic stroke. The functional receptor consists of two GluN1 subunits (a-h) and two GluN2 subunits (A/B/C/D), the expression of which are spatially and temporally regulated in pathological and physiological conditions. While the role of the GluN2A and GluN2B subunit in ischemic stroke has been well developed, the role of the GluN2C subunit in ischemia is not well understood. Following middle carotid artery occlusion (MCAO), GluN2C(-/-) male mice displayed similar volumes of infarct as wild-type (WT) mice...
October 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29073350/understanding-the-antibody-repertoire-in-neuropsychiatric-systemic-lupus-erythematosus-and-neuromyelitis-optica-spectrum-disorders-do-they-share-common-targets
#14
Simone Mader, Venkatesh Jeganathan, Yoshiyuki Arinuma, Yuichiro Fujieda, Irena Dujmovic, Jelena Drulovic, Yuka Shimizu, Yuko Sakuma, Joel N H Stern, Cynthia Aranow, Meggan Mackay, Shinsuke Yasuda, Tatsuya Atsumi, Shunsei Hirohata, Betty Diamond
OBJECTIVE: DWEYS-IgG cross-reactive with DNA and the N-methyl-D-aspartate receptor subunits GluN2A/GluN2B has been associated with neuropsychiatric systemic lupus erythematosus (NPSLE). DWEYS-IgG has not been investigated in demyelinating NPSLE (dNPSLE) or in another demyelinating disorder, Neuromyelitis Optica Spectrum Disorder (NMOSD), which is also a disease of young women and associated with aquaporin-4 (AQP4) or myelin oligodendrocyte glycoprotein (MOG) antibodies. We investigated the frequency of these brain-reactive antibodies in NPSLE, dNPSLE and NMOSD...
October 26, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29052618/a-role-for-prefrontal-cortical-nmda-receptors-in-murine-alcohol-heightened-aggression
#15
Emily L Newman, Miho Terunuma, Tiffany Wang, Nishani Hewage, Matthew B Bicakci, Stephen J Moss, Joseph F DeBold, Klaus A Miczek
Alcohol is associated with nearly half of all violent crimes committed in the United States; yet, a potential neural basis for this type of pathological aggression remains elusive. Alcohol may act on NMDA receptors (NMDARs) within cortical circuits to impede processing and to promote aggression. Here, male mice were characterized as alcohol-heightened (AHAs) or alcohol non-heightened aggressors (ANAs) during resident-intruder confrontations after self-administering 1.0 g/kg alcohol (6% w/v) or water. Alcohol produced a pathological-like pattern of aggression in AHAs; these mice shifted their bites to more vulnerable locations on the body of a submissive animal, including the anterior back and ventrum after consuming alcohol...
October 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29043770/a-novel-negative-allosteric-modulator-selective-for-glun2c-2d-containing-nmda-receptors-inhibits-synaptic-transmission-in-hippocampal-interneurons
#16
Sharon A Swanger, Katie M Vance, Timothy M Acker, Sommer S Zimmerman, John O DiRaddo, Scott J Myers, Christoffer Bundgaard, Cara A Mosley, Samantha L Summer, David S Menaldino, Henrik S Jensen, Dennis C Liotta, Stephen F Traynelis
N-Methyl-d-aspartate receptors (NMDARs) are ionotropic glutamate receptors that mediate excitatory synaptic transmission and have been implicated in numerous neurological disorders. NMDARs typically comprise two GluN1 and two GluN2 subunits. The four GluN2 subtypes (GluN2A-GluN2D) have distinct functional properties and gene expression patterns, which contribute to diverse functional roles for NMDARs in the brain. Here, we present a series of GluN2C/2D-selective negative allosteric modulators built around a N-aryl benzamide (NAB) core...
November 2, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29035834/synergistic-effect-of-mild-hypothermia-and-the-notch-inhibitor-dapt-against-post-stroke-seizures
#17
Guo-Shuai Yang, Xiao-Yan Zhou, Xue-Fang An, Xuan-Jun Liu, Yan-Jun Zhang, Dan Yu
Seizure is a serious complication of stroke, indicating poor prognosis. Notch signaling is associated with neuronal activity. Inhibition of Notch signaling suppresses seizure activity induced by kainic acid. The present study investigated the effect of the Notch inhibitor, DAPT, alone or in combination with mild hypothermia, on post-stroke seizures. A global cerebral ischemia (GCI) model was performed in Sprague Dawley (SD) male rats. Seizure activity was evaluated by the frequency of seizure attacks, seizure severity scores, and seizure discharges...
October 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29024713/a-lack-of-glun2a-containing-nmda-receptors-confers-a-vulnerability-to-redox-dysregulation-consequences-on-parvalbumin-interneurons-and-their-perineuronal-nets
#18
Romain Cardis, Jan-Harry Cabungcal, Daniella Dwir, Kim Q Do, Pascal Steullet
The GluN2A subunit of NMDA receptors (NMDARs) plays a critical role during postnatal brain development as its expression increases while Glun2B expression decreases. Mutations and polymorphisms in GRIN2A gene, coding for GluN2A, are linked to developmental brain disorders such as mental retardation, epilepsy, schizophrenia. Published data suggest that GluN2A is involved in maturation and phenotypic maintenance of parvalbumin interneurons (PVIs), and these interneurons suffer from a deficient glutamatergic neurotransmission via GluN2A-containing NMDARs in schizophrenia...
October 10, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28986871/selective-cell-surface-expression-of-triheteromeric-nmda-receptors
#19
Feng Yi, Stephen F Traynelis, Kasper B Hansen
The NMDA-type ionotropic glutamate receptors play pivotal roles in many brain functions, but are also involved in numerous brain disorders. Seven NMDA receptor subunits exist (GluN1, GluN2A-D, and GluN3A-B) that assemble into a diverse array of tetrameric receptor subtypes with distinct functional properties and physiological roles. Most NMDA receptors are composed of two GluN1 and two GluN2 subunits, which can assemble into four diheteromeric receptor subtypes composed of GluN1 and one type of GluN2 subunit (e...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986869/magnetofection%C3%A2-of-nmda-receptor-subunits-glun1-and-glun2a-expression-vectors-in-non-neuronal-host-cells
#20
Nadine Bruneau, Pierre Szepetowski
The functional study of reconstituted NMDA receptors (NMDARs) in host cells requires that the corresponding vectors for the expression of the NMDAR subunits are co-transfected with high efficiency. Magnetofection™ is a technology used to deliver nucleic acids to cells. It is driven and site-specifically guided by the attractive forces of magnetic fields acting on magnetic nanoparticles that are associated with nucleic acid vectors. In magnetofection™, cationic lipids form self-assembled complexes with the nucleic acid vectors of interest...
2017: Methods in Molecular Biology
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