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N-methyl-D-aspartate

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https://www.readbyqxmd.com/read/29457123/general-anesthesia-with-propofol-for-ovarian-teratoma-excision-associated-with-anti-n-methyl-d-aspartate-receptor-encephalitis
#1
Masami Sato, Hiroaki Yasumoto, Toshiyuki Arai
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder caused by production of anti-NMDAR antibodies that is often associated with ovarian teratoma and exhibits various manifestations including psychiatric symptoms, seizures, hypoventilation, and autonomic nerve instability. Patients with this disorder who receive early surgical tumor resection along with immunotherapy have better outcome than the rest of the patients. To establish an anesthetic plan, it is important to understand the pharmacological interaction between the anesthetic agents and the disabled NMDAR, because NMDAR is one of the major sites of action for commonly-used anesthetic agents...
2018: JA Clin Rep
https://www.readbyqxmd.com/read/29455177/nmdar-n-methyl-d-aspartate-receptor-encephalitis-in-a-patient-with-ms-multiple-sclerosis-a-rare-and-challenging-case
#2
Sadia Suleman, Qaiser Javed
We present a rare case of N-methyl-D-aspartate receptor (NMDAR) encephalitis in a 41-year-old Caucasian woman, who initially presented with prominent neuropsychiatric symptoms on the background of pre-existing multiple sclerosis. Here, the authors navigate the muddy water between neurology and psychiatry, describing the caveats of antibody testing with a misdiagnosed case of acute and transient psychotic episode. NMDAR encephalitis in MS is a rare condition, which can be easily confused with a new onset psychotic episode...
February 17, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29454156/the-glun2b-subunit-represents-a-major-functional-determinant-of-nmda-receptors-in-human-induced-pluripotent-stem-cell-derived-cortical-neurons
#3
Ioana Neagoe, Chang Liu, Alexander Stumpf, Yanmei Lu, Dongping He, Ross Francis, Jun Chen, Paul Reynen, Moulay Hicham Alaoui-Ismaili, Hirokazu Fukui
Abnormal signaling pathways mediated by N-methyl-d-aspartate receptors (NMDARs) have been implicated in the pathogenesis of various CNS disorders and have been long considered as promising points of therapeutic intervention. However, few efforts have been previously described concerning evaluation of therapeutic modulators of NMDARs and their downstream pathways in human neurons with endogenous expression of NMDARs. In the present study, we assessed expression, functionality, and subunit composition of endogenous NMDARs in human induced pluripotent stem cell (hiPSC)-derived cortical neurons (iCell Neurons and iCell GlutaNeurons)...
February 8, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29453445/alterations-in-interhemispheric-gamma-band-connectivity-are-related-to-the-emergence-of-auditory-verbal-hallucinations-in-healthy-subjects-during-nmda-receptor-blockade
#4
Thiebes Stephanie, Steinmann Saskia, Curic Stjepan, Polomac Nenad, Andreou Christina, Eichler Iris-Carola, Eichler Lars, Zöllner Christian, Gallinat Jürgen, Leicht Gregor, Mulert Christoph
Auditory verbal hallucinations (AVH) are a common positive symptom of schizophrenia. Excitatory-to-inhibitory (E/I) imbalance related to disturbed N-methyl-D-aspartate receptor (NMDAR) functioning has been suggested as a possible mechanism underlying altered connectivity and AVH in schizophrenia. The current study examined the effects of ketamine, a NMDAR antagonist, on glutamate-related mechanisms underlying interhemispheric gamma-band connectivity, conscious auditory perception during dichotic listening (DL), and the emergence of auditory verbal distortions and hallucinations (AVD/AVH) in healthy volunteers...
February 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29446949/positive-and-negative-allosteric-modulators-of-n-methyl-d-aspartate-nmda-receptors-structure-activity-relationships-and-mechanisms-of-action
#5
Erica S Burnell, Mark W Irvine, Guangyu Fang, Kiran Sapkota, David E Jane, Daniel T Monaghan
Excitatory activity in the CNS is predominately mediated by L-glutamate through several families of L-glutamate neurotransmitter receptors. Of these, the N-methyl-D-aspartate receptor (NMDAR) family has many critical roles in CNS function and in various neuropathological and psychiatric conditions. Until recently, the types of compounds available to regulate NMDAR function have been quite limited in terms of mechanism of action, subtype selectivity, and biological effect. However, several new classes of NMDAR agents have now been identified that are positive or negative allosteric modulators (PAMs and NAMs, respectively) with various patterns of NMDAR subtype selectivity...
February 15, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29446699/investigating-d-cycloserine-as-a-potential-pharmacological-enhancer-of-an-emotional-bias-learning-procedure
#6
Marcella L Woud, Simon E Blackwell, Susann Steudte-Schmiedgen, Michael Browning, Emily A Holmes, Catherine J Harmer, Jürgen Margraf, Andrea Reinecke
The partial N-methyl-D-aspartate receptor agonist d-cycloserine may enhance psychological therapies. However, its exact mechanism of action is still being investigated. Cognitive bias modification techniques allow isolation of cognitive processes and thus investigation of how they may be affected by d-cycloserine. We used a cognitive bias modification paradigm targeting appraisals of a stressful event, Cognitive Bias Modification-Appraisal, to investigate whether d-cycloserine enhanced the modification of appraisal, and whether it caused greater reduction in indices of psychopathology...
February 1, 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29446381/ketamine-blocks-bursting-in-the-lateral-habenula-to-rapidly-relieve-depression
#7
Yan Yang, Yihui Cui, Kangning Sang, Yiyan Dong, Zheyi Ni, Shuangshuang Ma, Hailan Hu
The N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine has attracted enormous interest in mental health research owing to its rapid antidepressant actions, but its mechanism of action has remained elusive. Here we show that blockade of NMDAR-dependent bursting activity in the 'anti-reward center', the lateral habenula (LHb), mediates the rapid antidepressant actions of ketamine in rat and mouse models of depression. LHb neurons show a significant increase in burst activity and theta-band synchronization in depressive-like animals, which is reversed by ketamine...
February 14, 2018: Nature
https://www.readbyqxmd.com/read/29444988/nmda-type-glutamate-receptor-activation-promotes-vascular-remodeling-and-pulmonary-arterial-hypertension
#8
Sébastien J Dumas, Gilles Bru-Mercier, Audrey Courboulin, Marceau Quatredeniers, Catherine Rücker-Martin, Fabrice Antigny, Morad K Nakhleh, Benoit Ranchoux, Elodie Gouadon, Maria-Candida Vinhas, Matthieu Vocelle, Nicolas Raymond, Peter Dorfmüller, Elie Fadel, Frédéric Perros, Marc Humbert, Sylvia Cohen-Kaminsky
Background -Excessive proliferation and apoptosis resistance in pulmonary vascular cells underlie vascular remodeling in pulmonary arterial hypertension (PAH). Specific treatments for PAH exist, mostly targeting endothelial dysfunction, but high pulmonary arterial pressure still causes heart failure and death. Pulmonary vascular remodeling may be driven by metabolic reprogramming of vascular cells to increase glutaminolysis and glutamate production. The N-methyl-D-aspartate receptor (NMDAR), a major neuronal glutamate receptor, is also expressed on vascular cells, but its role in PAH is unknown...
February 14, 2018: Circulation
https://www.readbyqxmd.com/read/29444764/clinical-radiological-pathological-correlation-in-an-unusual-case-of-refractory-epilepsy-a-two-year-journey-of-whodunit
#9
Deepak Menon, Ramshekhar N Menon, Chandrasekharan Kesavadas, Anita Mahadevan, Ashalatha Radhakrishnan, Sudheeran Kannoth, Pradeep P Nair, Mathew Abraham, Bejoy Thomas, Sanjeev V Thomas
New-onset refractory focal epilepsy poses significant challenges to the clinician in the absence of specific diagnostic biomarkers. Differential diagnoses based on imaging may be expanded by a veritable spectrum of peri-ictal imaging findings that may mask the underlying substrate. We report a 13-year-old girl who presented with refractory focal seizures of left parieto-occipital origin with cytotoxic gyral oedema noted over the same region on imaging. Despite an initial negative autoantibody profile, the patient was treated with immunosuppression, followed by serial relapses requiring immune-modulation...
February 14, 2018: Epileptic Disorders: International Epilepsy Journal with Videotape
https://www.readbyqxmd.com/read/29443773/anti-n-methyl-d-aspartate-receptor-encephalitis-associated-with-acute-toxoplasma-gondii-infection-a-case-report
#10
Xiaotang Cai, Hui Zhou, Yongmei Xie, Dan Yu, Zhiling Wang, Haitao Ren
RATIONALE: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has been recognized as the most frequent autoimmune encephalitis in children. Several infectious agents have been implicated in anti-NMDA encephalitis. PATIENT CONCERNS: A previously healthy immunocompetent 9-year-old girl first presented with seizures, headaches and vomiting. Cerebrospinal fluid and brain magnetic resonance imaging were normal. After one week onset, the patient gradually developed unexplained personality and behavior changes, accompanied by fever and seizures again...
February 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29440309/the-phosphodiesterase-2a-inhibitor-tak-915-ameliorates-cognitive-impairments-and-social-withdrawal-in-n-methyl-d-aspartate-receptor-antagonist-induced-rat-models-of-schizophrenia
#11
Masato Nakashima, Haruka Imada, Eri Shiraishi, Yuki Ito, Noriko Suzuki, Maki Miyamoto, Takahiko Taniguchi, Hiroki Iwashita
The pathophysiology of schizophrenia has been associated with glutamatergic dysfunction. Modulation of the glutamatergic signaling pathway, including N-methyl-D-aspartate (NMDA) receptors, can provide a new therapeutic target for schizophrenia. Phosphodiesterase 2A (PDE2A) is highly expressed in the forebrain, and is a dual substrate enzyme that hydrolyzes both cAMP and cGMP, which play pivotal roles as intracellular second messengers downstream of NMDA receptors. Here we characterize the in vivo pharmacological profile of a selective and brain penetrant PDE2A inhibitor, (N-{(1S)-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methoxyethyl}-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide) (TAK-915) as a novel treatment for schizophrenia...
February 13, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29439248/transient-receptor-potential-vanilloid-4-activation-induced-increase-in-glycine-activated-current-in-mouse-hippocampal-pyramidal-neurons
#12
Mengwen Qi, Chunfeng Wu, Zhouqing Wang, Li Zhou, Chen Men, Yimei Du, Songming Huang, Lei Chen, Ling Chen
BACKGROUND/AIMS: Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs) and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4) is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs...
February 7, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29438128/toxins-in-pain
#13
Fernanda C Cardoso, Mahadhi Hasan, Tianjiao Zhao, Richard J Lewis
PURPOSE OF REVIEW: Pain is a distressing protective sensory experience warning of actual or potential tissue damage. Natural toxins have evolved to exploit pain and related neuronal pathways to facilitate prey capture and for defence, often producing either numbness, paralysis or intense pain by selectively modulating ion channels and receptors in pain pathways. Understanding how toxins modulate pain pathways can enhance our understanding of the physiological and pathological basis of pain...
February 12, 2018: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/29433523/a-clinical-approach-to-new-onset-psychosis-associated-with-immune-dysregulation-the-concept-of-autoimmune-psychosis
#14
Souhel Najjar, Johann Steiner, Amanda Najjar, Karl Bechter
Growing data point to the overlap between psychosis and pathological processes associated with immunological dysregulation as well as inflammation. Notably, the recent discovery of antibodies against synaptic and neuronal cell membrane proteins such as anti-N-methyl-D-aspartate receptor provides more direct evidence of the etiological connection between autoimmunity and subsequent hazard of psychosis. Here, we advocate the use of term "autoimmune psychosis," as this term suggests that autoimmune disorders can masquerade as drug-resistant primary psychosis, and this subtype of psychosis has anatomical and immunological footprints in the brain, despite the frequent absence of structural abnormalities on conventional brain MRI...
February 13, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29429049/implication-of-genes-for-the-n-methyl-d-aspartate-nmda-receptor-in-substance-addictions
#15
REVIEW
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
https://www.readbyqxmd.com/read/29427922/psychotomimetic-like-behavioral-effects-of-memantine-in-the-mouse
#16
Nobue Kitanaka, Junichi Kitanaka, F Scott Hall, Yoshiro Kubota, Yumi Mimura, Sayaka Ogura, Yukiya Okada, George R Uhl, Motohiko Takemura
A single administration of mice with memantine (1-amino-3,5-dimethyladamantane), a glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist, induced stereotyped behaviors in dose- and time-dependent manners. The predominant behavioral component of the stereotypy was a continuous, exaggerated sniffing which was accompanied by persistent locomotion. In contrast, a psychostimulant methamphetamine (METH) predominantly induced a stereotyped biting and other forms of intense stationary stereotypical behaviors...
February 7, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29427172/up-regulation-of-ca-2-camkii-creb-signaling-in-salicylate-induced-tinnitus-in-rats
#17
Jiuhan Zhao, Biao Wang, Xiaohong Wang, Xiuli Shang
The purpose of the study was to investigate the changes of Ca2+/calmodulin-dependent protein kinases II (CaMKII)/cAMP response element-binding protein (CREB) signaling pathway in a rat tinnitus model. Eighteen Wistar rats were randomly divided into three groups: normal control (NC), normal saline (NS), and tinnitus model (TM) groups. Tinnitus model was induced by intraperitoneal injection of salicylate. The concentration of intracellular calcium level in auditory cortex cells was determined using Fura-2 acetoxymethyl ester (Fura-2 AM) method with fluorospectrophotometer...
February 9, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29426955/uncoupling-the-widespread-occurrence-of-anti-nmdar1-autoantibodies-from-neuropsychiatric-disease-in-a-novel-autoimmune-model
#18
Hong Pan, Bárbara Oliveira, Gesine Saher, Ekrem Dere, Daniel Tapken, Marina Mitjans, Jan Seidel, Janina Wesolowski, Debia Wakhloo, Christina Klein-Schmidt, Anja Ronnenberg, Kerstin Schwabe, Ralf Trippe, Kerstin Mätz-Rensing, Stefan Berghoff, Yazeed Al-Krinawe, Henrik Martens, Martin Begemann, Winfried Stöcker, Franz-Josef Kaup, Reinhard Mischke, Susann Boretius, Klaus-Armin Nave, Joachim K Krauss, Michael Hollmann, Fred Lühder, Hannelore Ehrenreich
Autoantibodies of the IgG class against N-methyl-D-aspartate-receptor subunit-NR1 (NMDAR1-AB) were considered pathognomonic for anti-NMDAR encephalitis. This view has been challenged by the age-dependent seroprevalence (up to >20%) of functional NMDAR1-AB of all immunoglobulin classes found in >5000 individuals, healthy or affected by different diseases. These findings question a merely encephalitogenic role of NMDAR1-AB. Here, we show that NMDAR1-AB belong to the normal autoimmune repertoire of dogs, cats, rats, mice, baboons, and rhesus macaques, and are functional in the NMDAR1 internalization assay based on human IPSC-derived cortical neurons...
February 9, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29425730/high-and-low-nightly-running-behavior-associates-with-nucleus-accumbens-n-methyl-d-aspartate-receptor-nmdar-nr1-subunit-expression-and-nmdar-functional-differences
#19
Kolter B Grigsby, Cathleen M Kovarik, George E Rottinghaus, Frank W Booth
The extent to which N-Methyl-D-aspartate (NMDA) receptors facilitate the motivation to voluntarily wheel-run in rodents has yet to be determined. In so, we utilized female Wistar rats selectively bred to voluntarily run high (HVR) and low (LVR) nightly distances in order to examine if endogenous differences in nucleus accumbens (NAc) NMDA receptor expression and function underlies the propensity for high or low motivation to voluntarily wheel-run. 12-14 week old HVR and LVR females were used to examine: 1.) NAc mRNA and protein expression of NMDA subunits NR1, NR2A and NR2B; 2...
February 6, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29423241/novel-rare-variations-in-genes-that-regulate-developmental-change-in-n-methyl-d-aspartate-receptor-in-patients-with-schizophrenia
#20
Akane Yoshikawa, Fumichika Nishimura, Aya Inai, Yosuke Eriguchi, Masaki Nishioka, Atsuhiko Takaya, Mamoru Tochigi, Yoshiya Kawamura, Tadashi Umekage, Kayoko Kato, Tsukasa Sasaki, Kiyoto Kasai, Chihiro Kakiuchi
The mechanism underlying the vulnerability to developing schizophrenia (SCZ) during adolescence remains elusive. Hypofunction of N-methyl-d-aspartate receptors (NMDARs) has been implicated in the pathophysiology of SCZ. During development, the composition of synaptic NMDARs dramatically changes from NR2B-containing NMDARs to NR2A-containing NMDARs through the phosphorylation of NR2B S1480 or Y1472 by CDK5, CSNK2A1, and EphB2, which plays a pivotal role in the maturation of neural circuits. We hypothesized that the dysregulation of developmental change in NMDARs could be involved in the onset of SCZ...
2018: Human Genome Variation
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