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Alessio Travaglia, Adam B Steinmetz, Janelle M Miranda, Cristina M Alberini
Episodic memories in early childhood are rapidly forgotten, a phenomenon that is associated with "infantile amnesia," the inability of adults to remember early-life experiences. We recently showed that early aversive contextual memory in infant rats, which is in fact rapidly forgotten, is actually not lost, as reminders presented later in life reinstate a long-lasting and context-specific memory. We also showed that the formation of this infantile memory recruits in the hippocampus mechanisms typical of developmental critical periods...
April 2018: Learning & Memory
Marta Portero-Tresserra, Margarita Martí-Nicolovius, Mireia Tarrés-Gatius, Ana Candalija, Gemma Guillazo-Blanch, Anna Vale-Martínez
RATIONALE: Aging is characterized by a decrease in N-methyl-D-aspartate receptors (NMDARs) in the hippocampus, which might be one of the factors involved in the age-dependent cognitive decline. D-Cycloserine (DCS), a partial agonist of the NMDAR glycine recognition site, could improve memory deficits associated to neurodegenerative disorders and cognitive deficits observed in normal aging. OBJECTIVES AND METHODS: The aim of the present study was to explore whether DCS would reverse age-dependent memory deficits and decreases in NMDA receptor subunits (GluN1, GluN2A, and GluN2B) and the presynaptic protein synaptophysin in Wistar rats...
February 28, 2018: Psychopharmacology
Feng Yi, Linda G Zachariassen, Katherine N Dorsett, Kasper B Hansen
NMDA-type glutamate receptors mediate excitatory synaptic transmission in the central nervous system and play critical roles in many neuronal processes. The physiological roles of NMDA receptors are shaped by their functional properties, which are highly dependent on subunit composition. Most NMDA receptors are assembled from two GluN1 and two GluN2 subunits, but diversity in subunit composition is made possible by eight GluN1 splice variants (i.e. isoforms) and four distinct GluN2 subunits (GluN2A-D). We demonstrate using FRET-FLIM that GluN1-1a and GluN1-1b isoforms, which includes or lacks residues encoded by exon 5, form triheteromeric GluN1-1a/GluN1-1b/GluN2A (1a/1b/2A) and GluN1-1a/GluN1-1b/GluN2B (1a/1b/2B) receptors...
February 26, 2018: Molecular Pharmacology
J Jane Zhang, Josué Haubrich, Matteo Bernabo, Peter S B Finnie, Karim Nader
Reconsolidation, a process by which long-term memories are rendered malleable following retrieval, has been shown to occur across many different species and types of memory. However, there are conditions under which memories do not reconsolidate, and the reasons for this are poorly understood. One emerging theory is that these boundary conditions are mediated by a form of metaplasticity: cellular changes through which experience can affect future synaptic plasticity. We review evidence that N-methyl-D-aspartate receptors (NMDARs) might contribute to this phenomenon, and hypothesize that resistance to memory destabilization may be mediated by the ratio of GluN2A/GluN2B subunits that make up these receptors...
February 20, 2018: Neurobiology of Learning and Memory
Yoshiyuki Arinuma
PURPOSE OF REVIEW: Neuropsychiatric manifestations are one of the fatal complications in patients with systemic lupus erythematosus (SLE). However, the diagnosis and monitoring of that aspect of SLE is still challenging, as there are no reliable biomarkers linked to central nervous system (CNS) damage. This review emphasizes potential candidate autoantibodies that appear to be associated with development of behavioral and psychiatric manifestations in SLE patients. RECENT FINDINGS: Developments in the pathogenesis in SLE, not surprising for this immune disorder, point to specific, autoantibody toxicity...
February 22, 2018: Current Opinion in Neurology
Mi Zhou, Zhao Liu, Jia Yu, Shuiming Li, Min Tang, Li Zeng, Haiyang Wang, Hong Xie, Li Peng, Haojun Huang, Chanjuan Zhou, Peng Xie, Jian Zhou
The amygdala plays a key role in the pathophysiology of depression, but the molecular mechanisms underlying amygdalar hyperactivity in depression remain unclear. In this study, we used a chronic mild stress (CMS) protocol to separate susceptible and insusceptible rat subgroups. Proteomes in the amygdalae were analyzed differentially across subgroups based on labeling with isobaric tags for relative and absolute quantitation (iTRAQ) combined with mass spectrometry. Of 2562 quantified proteins, 102 were differentially expressed...
February 13, 2018: Neuroscience
Sarah A Monaco, Brielle R Ferguson, Wen-Jun Gao
Glycogen synthase kinase 3β (GSK3β) is a highly conserved serine/threonine kinase that has been implicated in both psychiatric and neurodegenerative diseases including schizophrenia, bipolar disorder, and Alzheimer's disease; therefore regulating its activity has become an important strategy for treatment of cognitive impairments in these disorders. This study examines the effects of lithium on GSK3β and its interaction with β-catenin and NMDA receptors within the prefrontal cortex. Lithium, a clinically relevant drug commonly prescribed as a mood stabilizer for psychiatric disorders, significantly increased levels of phosphorylated GSK3β serine 9, an inhibitory phosphorylation site, and decreased β-catenin ser33/37/thr41 phosphorylation in vitro , indicating GSK3β inhibition and reduced β-catenin degradation...
2018: Frontiers in Cellular Neuroscience
Jiali Chen, Yunlong Ma, Rongli Fan, Zhongli Yang, Ming D Li
Drug dependence is a chronic brain disease with harmful consequences for both individual users and society. Glutamate is a primary excitatory neurotransmitter in the brain, and both in vivo and in vitro experiments have implicated N-methyl-D-aspartate (NMDA) receptor, a glutamate receptor, as an element in various types of addiction. Recent findings from genetics-based approaches such as genome-wide linkage, candidate gene association, genome-wide association (GWA), and next-generation sequencing have demonstrated the significant association of NMDA receptor subunit genes such as GluN3A, GluN2B, and GluN2A with various addiction-related phenotypes...
February 10, 2018: Molecular Neurobiology
Bernhard Wünsch, Louisa Temme, Dirk Schepmann, Julian A Schreiber, Bastian Frehland
Since only a few studies investigated the affinity and functional activity of NMDA receptor open channel blockers under same assay conditions, a comparative study of common open channel blockers is of major interest. The pharmacological activity of MK-801, phencyclidine, dexoxadrol, etoxadrol, (S)- and (R)-ketamine, dextromethorphan, memantine and amantadine was analyzed under same uniform assay conditions. The affinity towards the PCP and ifenprodil binding sites was recorded in radioligand binding assays...
January 27, 2018: ChemMedChem
S Y Yau, Luis Bettio, M Vetrici, A Truesdell, C Chiu, J Chiu, E Truesdell, B R Christie
Fragile X Syndrome (FXS) is the most common inherited cause of intellectual disability, and is the leading known single-gene cause of autism spectrum disorder. FXS patients display varied behavioural deficits that include mild to severe cognitive impairments in addition to mood disorders. Currently there is no cure for this condition, however minocycline is becoming commonly prescribed as a treatment for FXS patients. Minocycline has been reported to alleviate social behavioural deficits, and improve verbal functioning in patients with FXS; however, its mode of action is not well understood...
January 20, 2018: Neurobiology of Disease
Xiaoyu Hu, Jinghua Yang, Yaling Sun, Xiang Gao, Lijin Zhang, Yingqi Li, Miao Yu, Shiyu Liu, Xiaobo Lu, Cuihong Jin, Shengwen Wu, Yuan Cai
Studies have reported that lanthanum chloride (LaCl3) can across the blood-brain barrier, accumulate in the brain and affect the spatial learning and memory abilities. However, the potential mechanism that LaCl3-induced neurotoxic effects has not yet been defined. Glutamate (Glu) is a vital excitatory neurotransmitter, and the excessive Glu accumulation in extracellular space can induce excitatory neurotoxicity. This study was designed to research the influence of LaCl3 on the spatial learning and memory abilities of rats and to discuss the possible mechanism underlying this effect regarding the extracellular Glu concentration, the Glu-glutamine (Gln) cycle and the N-methyl-D-aspartate (NMDA) receptors...
January 15, 2018: Food and Chemical Toxicology
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
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
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
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...
March 2018: Neuromolecular Medicine
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
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
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
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
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
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