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https://www.readbyqxmd.com/read/29241198/fam3a-protects-against-glutamate-induced-toxicity-by-preserving-calcium-homeostasis-in-differentiated-pc12-cells
#1
Qing Song, Wen-Li Gou, Yu-Liang Zou
BACKGROUND/AIMS: Stroke is the leading cause of adult disability, and glutamate-induced dysregulation of intracellular Ca2+ homeostasis is a key mechanism. FAM3A is the first member of the family with sequence similarity 3 (FAM3) gene family, and its biological function remains largely unknown. We have recently reported that FAM3A exerts protective effects against oxidative stress and mitochondrial dysfunction in HT22 cells. METHODS: Here, we investigated the protective effects of FAM3A using a glutamate-induced neuronal injury model in nerve growth factor (NGF)-differentiated PC12 cells...
December 12, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29232014/mutations-of-the-glycine-cleavage-system-genes-possibly-affect-the-negative-symptoms-of-schizophrenia-through-metabolomic-profile-changes
#2
Akane Yoshikawa, Fumichika Nishimura, Aya Inai, Yosuke Eriguchi, Masaki Nishioka, Atsuhiko Takaya, Mamoru Tochigi, Yoshiya Kawamura, Tadashi Umekage, Kayoko Kato, Tsukasa Sasaki, Yoshiaki Ohashi, Kazuya Iwamoto, Kiyoto Kasai, Chihiro Kakiuchi
AIM: Hypofunction of N-methyl-D-aspartate receptors (NMDARs) may contribute to the pathophysiology of schizophrenia (SCZ). Recently, the glycine cleavage system (GCS) was shown to affect NMDAR function in the brain. GCS functional defects cause nonketotic hyperglycinemia (NKH), the atypical phenotype of which presents psychiatric symptoms similar to SCZ. Here, we examined the involvement of GCS in SCZ. METHODS: First, to identify the rare variants and the exonic deletions, we re-sequenced all the coding exons and the splice sites of four GCS genes (GLDC, AMT, GCSH, DLD) in 474 patients with SCZ and 475 controls and performed multiplex ligation-dependent probe amplification (MLPA) analysis in SCZ...
December 12, 2017: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/29230960/ciq-a-positive-allosteric-modulator-of-glun2c-d-containing-n-methyl-d-aspartate-receptors-rescues-striatal-synaptic-plasticity-deficit-in-a-mouse-model-of-parkinson-s-disease
#3
Mona Nouhi, Xiaoqun Zhang, Ning Yao, Karima Chergui
AIMS: To investigate if CIQ, a positive allosteric modulator of N-methyl-d-aspartate receptors (NMDARs) containing GluN2C/D subunits, rescues the loss of long-term potentiation (LTP) and forelimb-use asymmetry in a mouse model of Parkinson's disease (PD). METHODS: We have used electrophysiology in brain slices and the cylinder test to examine the effect of CIQ on glutamatergic synaptic transmission, synaptic plasticity, and forelimb-use in the unilateral 6-hydroxydopamine-lesion mouse model of PD...
December 11, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29229209/randomized-double-blind-placebo-controlled-dose-escalation-study-investigation-of-the-safety-pharmacokinetics-and-antihyperalgesic-activity-of-l-4-chlorokynurenine-in-healthy-volunteers
#4
Mark Wallace, Alexander White, Kathy A Grako, Randal Lane, Allen Jo Cato, H Ralph Snodgrass
BACKGROUND AND AIMS: Neuropathic pain is a significant medical problem needing more effective treatments with fewer side effects. Overactive glutamatergic transmission via N-methyl-d-aspartate receptors (NMDARs) are known to play a role in central sensitization and neuropathic pain. Although ketamine, a NMDAR channel-blocking antagonist, is often used for neuropathic pain, its side-effect profile and abusive potential has prompted the search for a safer effective oral analgesic. A novel oral prodrug, AV-101 (l-4 chlorokynurenine), which, in the brain, is converted into one of the most potent and selective GlyB site antagonists of the NMDAR, has been demonstrated to be active in animal models of neuropathic pain...
October 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29228131/synaptic-potentiation-at-basal-and-apical-dendrites-of-hippocampal-pyramidal-neurons-involves-activation-of-a-distinct-set-of-extracellular-and-intracellular-molecular-cues
#5
Patrycja Brzdak, Olga Wójcicka, Monika Zareba-Koziol, Daniel Minge, Christian Henneberger, Jakub Wlodarczyk, Jerzy W Mozrzymas, Tomasz Wójtowicz
In the central nervous system, several forms of experience-dependent plasticity, learning and memory require the activity-dependent control of synaptic efficacy. Despite substantial progress in describing synaptic plasticity, mechanisms related to heterogeneity of synaptic functions at local circuits remain elusive. Here we studied the functional and molecular aspects of hippocampal circuit plasticity by analyzing excitatory synapses at basal and apical dendrites of mouse hippocampal pyramidal cells (CA1 region) in acute brain slices...
December 8, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29226117/pediatric-anti-n-methyl-d-aspartate-receptor-encephalitis-a-review-with-pooled-analysis-and-critical-care-emphasis
#6
REVIEW
Kenneth E Remy, Jason W Custer, Joshua Cappell, Cortney B Foster, Nan A Garber, L Kyle Walker, Liliana Simon, Dayanand Bagdure
Purpose: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is being recognized with increasing frequency among children. Given the paucity of evidence to guide the critical care management of these complex patients, we provide a comprehensive review of the literature with pooled analysis of published case reports and case series. Methods: We performed a comprehensive literature search using PubMed, Scopus, EMBASE, and Web of Science for relevant published studies...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/29225043/neurogranin-in-the-nucleus-accumbens-regulates-nmda-receptor-tolerance-and-motivation-for-ethanol-seeking
#7
Ashlie N Reker, Alfredo Oliveros, John M Sullivan, Lailun Nahar, David J Hinton, Taehyun Kim, Robert C Bruner, Doo-Sup Choi, Nicholas E Goeders, Hyung W Nam
Dysfunction of N-methyl-D-aspartate receptor (NMDAR) signaling in the nucleus accumbens (NAc) has been implicated in the pathophysiology of alcohol use disorders (AUD). Neurogranin (Ng), a calmodulin-binding protein, is exclusively expressed in the post-synapse, and mediates NMDAR driven synaptic plasticity by regulating the calcium-calmodulin (Ca2+-CaM) pathway. To study the functional role of Ng in AUD, we administrated behavior tests including Pavlovian instrument transfer (PIT), operant conditioning, and rotarod test using Ng null mice (Ng-/- mice)...
December 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29224722/nrap-1-is-a-presynaptically-released-nmda-receptor-auxiliary-protein-that-modifies-synaptic-strength
#8
Ning Lei, Jerry E Mellem, Penelope J Brockie, David M Madsen, Andres V Maricq
NMDA receptors (NMDARs) are a subtype of postsynaptic ionotropic glutamate receptors that function as molecular coincidence detectors, have critical roles in models of learning, and are associated with a variety of neurological and psychiatric disorders. To date, no auxiliary proteins that modify NMDARs have been identified. Here, we report the identification of NRAP-1, an auxiliary protein in C. elegans that modulates NMDAR function. NMDAR-mediated currents were eliminated in nrap-1 mutants, as was NMDA-dependent behavior...
December 1, 2017: Neuron
https://www.readbyqxmd.com/read/29222403/common-pathophysiology-in-multiple-mouse-models-of-pitt-hopkins-syndrome
#9
Courtney Thaxton, Alexander D Kloth, Ellen P Clark, Sheryl S Moy, Raymond A Chitwood, Benjamin D Philpot
Mutations or deletions of the transcription factor TCF4 are linked to Pitt-Hopkins syndrome (PTHS) and schizophrenia, suggesting that the precise pathogenic mutations dictate cellular, synaptic, and behavioral consequences. Here we generated two novel mouse models of PTHS-one that mimics the most common pathogenic TCF4 point mutation (human R580W, mouse R579W) and one that deletes three pathogenic arginines-and explored phenotypes of these lines alongside models of pan-cellular or CNS-specific heterozygous Tcf4 disruption...
December 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29218821/activity-dependent-control-of-nmda-receptor-subunit-composition-at-hippocampal-mossy-fibre-synapses
#10
Mario Carta, Bettadapura N Srikumar, Adam Gorlewicz, Nelson Rebola, Christophe Mulle
Single neurons express NMDARs with distinct subunit composition and biophysical properties which can be segregated in an input-specific manner. The dynamic control of the heterogeneous distribution of synaptic NMDARs is crucial to control input-dependent synaptic integration and plasticity. In hippocampal CA3 pyramidal cells (CA3 PCs) from mice of both sexes, we found that mossy fibre (Mf) synapses display a markedly lower proportion of GluN2B containing NMDARs than associative/commissural synapses. The mechanism involved in such heterogeneous distribution of GluN2B subunits is not known...
December 7, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29205377/adenosine-a2a-receptors-are-required-for-glutamate-mglur5-and-dopamine-d1-receptor-evoked-erk1-2-phosphorylation-in-rat-hippocampus-involvement-of-nmda-receptor
#11
Paraskevi Krania, Eleni Dimou, Maria Bantouna, Stylianos Kouvaros, Eirini Tsiamaki, Costas Papatheodoropoulos, Konstantinos Sarantis, Fevronia Angelatou
Interaction between mGluR5 and NMDA receptors (NMDAR) is vital for synaptic plasticity and cognition. We recently demonstrated that stimulation of mGluR5 enhances NMDAR-responses in hippocampus by phosphorylating NR2B(Tyr1472) subunit, and this reaction was enabled by adenosine A2A receptors(A2A R) (Sarantis et al.2015). In this study, by using in vitro phosphorylation and western blot analysis in hippocampal slices of male Wistar rats, we show, that mGluR5 stimulation or mGluR5/NMDARs co-stimulation, synergistically activate ERK1/2 signaling leading to c-Fos expression...
December 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29199135/deficits-in-synaptic-function-occur-at-medial-perforant-path-dentate-granule-cell-synapses-prior-to-schaffer-collateral-ca1-pyramidal-cell-synapses-in-the-novel-tgf344-alzheimer-s-disease-rat-model
#12
Lindsey A Smith, Lori L McMahon
Alzheimer's disease (AD) pathology begins decades prior to onset of clinical symptoms, and the entorhinal cortex and hippocampus are among the first and most extensively impacted brain regions. The TgF344-AD rat model, which more fully recapitulates human AD pathology in an age-dependent manner, is a next generation preclinical rodent model for understanding pathophysiological processes underlying the earliest stages of AD (Cohen et al., 2013). Whether synaptic alterations occur in hippocampus prior to reported learning and memory deficit is not known...
December 1, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29197887/important-differential-in-a-patient-presenting-with-neuropsychiatric-symptoms-anti-n-methyl-d-aspartate-receptor-encephalitis
#13
J M Low
Anti-N-Methyl-D-Aspartate receptor (NMDAR) encephalitis is an immune mediated condition, which remains relatively unknown in Malaysia outside tertiary hospitals with neurology unit. It is often misdiagnosed as a psychiatric illness before definitive treatment is instituted. We report here an 18-year-old man who initially presented to the psychiatry unit before he was subsequently diagnosed as having anti-NMDAR encephalitis. To our knowledge, this is the first reported case of anti-NMDAR encephalitis in the east coast of Peninsular Malaysia...
October 2017: Medical Journal of Malaysia
https://www.readbyqxmd.com/read/29196318/inactivation-of-nmda-receptors-in-the-ventral-tegmental-area-during-cocaine-self-administration-prevents-glua1-up-regulation-but-with-paradoxical-increases-in-cocaine-seeking-behavior
#14
Daniel Guzman, Maria B Carreira, Allyson K Friedman, Megumi Adachi, Rachael L Neve, Lisa M Monteggia, Ming-Hu Han, Christopher W Cowan, David W Self
Cocaine self-administration increases expression of GluA1 subunits in ventral tegmental area (VTA) dopamine neurons that subsequently enhance the motivation for cocaine. This increase in GluA1 may be dependent on concomitant NMDA receptor (NMDAR) activation during self-administration, similar to cocaine-induced LTP in the VTA. In this study, we used viral-mediated expression of a dominant negative GluN1 subunit (HSV-dnGluN1) in VTA neurons to study the effect of transient NMDAR inactivation on the GluA1 increases induced by chronic cocaine self-administration in male rats...
December 1, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29196183/nmda-receptor-antagonist-rodent-models-for-cognition-in-schizophrenia-and-identification-of-novel-drug-treatments-an-update
#15
REVIEW
Daniela Cadinu, Ben Grayson, Giovanni Podda, Michael K Harte, Nazanin Doostdar, Joanna C Neill
Negative and cognitive deficit symptoms in schizophrenia remain an unmet clinical need. Improved understanding of the neuro- and psychopathology of cognitive dysfunction in the illness is urgently required to enhance the development of new improved therapeutic strategies. Careful validation of animal models that mimic the behaviour and pathology of complex psychiatric disorders is an essential step towards this goal. Non-competitive NMDAR (N-Methyl-d-aspartate receptor) antagonists e.g. phencyclidine (PCP), ketamine and dizocilpine (MK-801) can effectively replicate certain aspects of negative and cognitive deficits associated with schizophrenia in animals...
November 28, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29194436/characterisation-of-the-pathogenic-effects-of-the-in-vivo-expression-of-an-als-linked-mutation-in-d-amino-acid-oxidase-phenotype-and-loss-of-spinal-cord-motor-neurons
#16
Nazanin Rahmani Kondori, Praveen Paul, Jacqueline P Robbins, Ke Liu, John C W Hildyard, Dominic J Wells, Jacqueline S de Belleroche
Amyotrophic lateral sclerosis (ALS) is the most common adult-onset neuromuscular disorder characterised by selective loss of motor neurons leading to fatal paralysis. Current therapeutic approaches are limited in their effectiveness. Substantial advances in understanding ALS disease mechanisms has come from the identification of pathogenic mutations in dominantly inherited familial ALS (FALS). We previously reported a coding mutation in D-amino acid oxidase (DAOR199W) associated with FALS. DAO metabolises D-serine, an essential co-agonist at the N-Methyl-D-aspartic acid glutamate receptor subtype (NMDAR)...
2017: PloS One
https://www.readbyqxmd.com/read/29193273/activation-of-caspase-6-and-cleavage-of-caspase-6-substrates-is-an-early-event-in-nmda-receptor-mediated-excitotoxicity
#17
Kimberly D Girling, Marie-Josee Demers, Jean Laine, Shu Zhang, Yu Tian Wang, Rona K Graham
Excitotoxicity, due to overstimulation of N-methyl D-aspartate receptors (NMDARs), has a pivotal role in many neurological disorders. However, NMDAR antagonists often cause side effects, and identifying more druggable therapeutic targets for NMDAR excitotoxicity is an important goal. Activation of caspases is a downstream effect of excitotoxicity that may be critically involved in NMDAR-mediated cell death. Caspase-6 (casp6) in particular has been shown to play a key role in the pathogenesis of stroke, Huntington disease, and Alzheimer disease...
November 29, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29187660/-nmda-receptor-and-its-role-in-cardiovascular-diseases
#18
Jinyan Xie, Kui Hong
Cardiovascular disease is the main threat to human health, which is one of the important causes of death in worldwide. N-methyl-D-aspartate receptor (NMDAR) is one of crucial ionic glutamate receptors. The physiology and pharmacology function of the composition of NMDAR are very complicated. Researches have shown that NMDAR with a high permeability to calcium and a unique feature of controlling numerous calcium-dependent processes. NMDAR affects the occurrence and development of cardiovascular disease such as hypertension, arrhythmia, myocardial infarction...
November 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29186977/ictal-rhythmic-alpha-sinusoidal-waves-in-3-cases-of-anti-nmdar-encephalitis
#19
Ailiang Miao, Xiaoshan Wang
Previous studies have shown that extreme delta brush and high beta/delta power ratio on electroencephalogram are suggestive of anti- N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. Here we report 3 anti-NMDAR encephalitis patients with ictal rhythmic alpha sinusoidal waves in temporal regions, which suggested electrographic seizures in anti-NMDAR encephalitis and indicated potential for seizure occurrence in the future. Rhythmic alpha sinusoidal waves may be an electrographic feature and helpful in distinguishing anti-NMDAR encephalitis...
November 1, 2017: Clinical EEG and Neuroscience: Official Journal of the EEG and Clinical Neuroscience Society (ENCS)
https://www.readbyqxmd.com/read/29183618/encephalitis-associated-with-antibodies-against-the-nmda-receptor
#20
REVIEW
Mar Guasp, Josep Dalmau
The encephalitis associated with antibodies against the N-methyl-D-aspartate receptor (NMDAR) is characterized by the presence of antibodies against the GluN1 subunit of this receptor, resulting in symptoms that are similar to those observed in models of genetic or pharmacologic reduction of NMDARs. Patients are usually young adults, predominantly women, and children who develop, in a sequential manner, rapidly progressive symptoms including psychosis, abnormal movements, autonomic dysfunction, and coma. Epileptic seizures are variable and can occur throughout the course of the disease...
November 25, 2017: Medicina Clínica
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