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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/29454833/towards-resolving-the-presynaptic-nmda-receptor-debate
#3
REVIEW
Guy Bouvier, Rylan S Larsen, Antonio Rodríguez-Moreno, Ole Paulsen, P Jesper Sjöström
In the classical view, postsynaptic NMDA receptors (NMDARs) trigger Hebbian plasticity via Ca2+ influx. However, unconventional presynaptic NMDARs (preNMDARs) which regulate both long-term and short-term plasticity at several synapse types have also been found. A lack of sufficiently specific experimental manipulations and a poor understanding of how preNMDARs signal have contributed to long-standing controversy surrounding these receptors. Although several prior studies linked preNMDARs to neocortical timing-dependent long-term depression (tLTD), a recent study argues that the NMDARs are actually postsynaptic and signal metabotropically, that is, without Ca2+ ...
January 20, 2018: Current Opinion in Neurobiology
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
#4
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
#5
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
#6
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/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/29443773/anti-n-methyl-d-aspartate-receptor-encephalitis-associated-with-acute-toxoplasma-gondii-infection-a-case-report
#9
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/29438741/different-mechanisms-underlie-stress-induced-changes-in-plasticity-and-metaplasticity-in-the-prefrontal-cortex-of-juvenile-and-adult-animals
#10
Tala Khazen, Kuldeep Shrivastava, Reem Jada, Ossama Abu Hatoum, Mouna Maroun
Metaplasticity is the dynamic regulation of the ability to induce activity-dependent synaptic plasticity and is governed by the prior history of the synapses. Previous reports by others and us have shown that behavioral stress induces a form of emotional metaplasticity that affects the ability to induce LTP in the subiculum-medial prefrontal cortex pathway, which depends on NMDA receptors (NMDAr). However, studies addressing the effects of stress on LTP and metaplasticity have mainly focused on the adult animal...
February 10, 2018: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29438442/the-sirna-mediated-knockdown-of-glun3a-in-46c-derived-neural-stem-cells-affects-mrna-expression-levels-of-neural-genes-including-known-iglur-interactors
#11
Svenja Pachernegg, Sebastian Eilebrecht, Elke Eilebrecht, Hendrik Schöneborn, Sebastian Neumann, Arndt G Benecke, Michael Hollmann
For years, GluN3A was solely considered to be a dominant-negative modulator of NMDARs, since its incorporation into receptors alters hallmark features of conventional NMDARs composed of GluN1/GluN2 subunits. Only recently, increasing evidence has accumulated that GluN3A plays a more diversified role. It is considered to be critically involved in the maturation of glutamatergic synapses, and it might act as a molecular brake to prevent premature synaptic strengthening. Its expression pattern supports a putative role during neural development, since GluN3A is predominantly expressed in early pre- and postnatal stages...
2018: PloS One
https://www.readbyqxmd.com/read/29426955/uncoupling-the-widespread-occurrence-of-anti-nmdar1-autoantibodies-from-neuropsychiatric-disease-in-a-novel-autoimmune-model
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/29417305/anti-nmda-receptor-encephalitis-presenting-as-postpartum-psychosis-a-clinical-description-and-review
#15
Mukku Shiva Shanker Reddy, Harish Thippeswamy, Sundarnag Ganjekar, Madhu Nagappa, Anita Mahadevan, H R Arvinda, Prabha S Chandra, Arun B Taly
Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is increasingly being recognised to be associated with protean neuropsychiatric manifestations. Anti-NMDAR encephalitis is considered to be the most common amongst the autoimmune-mediated encephalitic disorders. It is caused by the autoantibodies against GluN1 subunits of N-methyl-D-aspartate (NMDA) receptor and manifests with prominent psychiatric symptoms, especially during the initial phase of illness. Literature anti-NMDAR encephalitis presenting with postpartum psychosis is scant...
February 7, 2018: Archives of Women's Mental Health
https://www.readbyqxmd.com/read/29417050/d-amino-acid-oxidase-plg72-interaction-and-d-serine-modulation
#16
REVIEW
Loredano Pollegioni, Luciano Piubelli, Gianluca Molla, Elena Rosini
pLG72 is a small, primate-specific protein of 153 amino acids. It is the product of the G72 gene, expressed in testis, spinal cord, and brain. The presence of G72 transcript and pLG72 has recurrently been called into question, however G72 mRNA and pLG72 protein levels were higher in blood and brain of patients with schizophrenia than in healthy controls. On the one hand, the SNP rs2391191 corresponding to the R30K substitution in pLG72 was genetically linked to schizophrenia, reduced thickness of the brain cortex in schizophrenia-affected individuals, and altered memory function...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29413527/the-role-of-serine-racemase-in-the-pathophysiology-of-brain-disorders
#17
Joseph T Coyle, Darrick T Balu
The N-methyl-d-aspartate receptor (NMDAR) is unique in requiring two agonists to bind simultaneously to open its cation channel: the neurotransmitter, glutamate, and the coagonists, glycine, or d-serine. The Snyder laboratory was the first to clone serine racemase (SR), the enzyme that synthesizes d-serine, and to localize it immunocytochemically. Our laboratory has focused on the role of d-serine in brain disorders. Silencing the expression of SR, a risk gene for schizophrenia (SCZ), in mice (SR-/-), results in a phenotype that closely resembles SCZ including: cortical atrophy, reduced dendritic spine density and complexity, downregulation of parvalbumin-positive cortical GABAergic neurons, and cognitive impairments...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29413523/anti-nmda-receptor-encephalitis-clinical-features-and-basic-mechanisms
#18
David R Lynch, Amy Rattelle, Yi Na Dong, Kylie Roslin, Amy J Gleichman, Jessica A Panzer
In slightly more than 10 years, anti-NMDA receptor (NMDAR) encephalitis has changed from a rare paraneoplastic syndrome to the most common cause of nonviral encephalitis. It presents fulminantly with progressive psychosis, seizures, and autonomic dysfunction, leading to death if untreated. However, rapid recognition and treatment can lead to survival and a return to baseline levels of functioning in many patients. While initially associated with ovarian teratomas, it is now associated with other tumors and can reflect a postviral event...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29406578/n-methyl-d-aspartate-receptor-antibody-production-from-germinal-center-reactions-therapeutic-implications
#19
Mateusz Makuch, Robert Wilson, Adam Al-Diwani, James Varley, Anne-Katrin Kienzler, Jennifer Taylor, Antonio Berretta, Darren Fowler, Belinda Lennox, M Isabel Leite, Patrick Waters, Sarosh R Irani
Introduction N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis is mediated by IgG-autoantibodies directed against the NR1-subunit of the NMDAR. Around 20% of patients have an underlying ovarian teratoma, and the condition responds to early immunotherapies and ovarian teratoma removal. However, despite clear therapeutic relevance, mechanisms of NR1-IgG production and the contribution of germinal center B cells to NR1-IgG levels are unknown. Methods Clinical data and longitudinal paired serum NR1-reactive IgM and IgG levels from ten patients with NMDAR-antibody encephalitis were determined...
February 6, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29405453/electrogenic-nmda-receptor-signaling-enhances-binaural-responses-in-the-adult-brainstem
#20
Ida Siveke, Julian J Ammer, Sarah A Gleiss, Benedikt Grothe, Christian Leibold, Felix Felmy
In sensory systems the neuronal representation of external stimuli is enhanced along the sensory pathway. In the auditory system, strong enhancement of binaural information takes place between the brainstem and the midbrain, however the underlying cellular mechanisms are unknown. Here we investigated the transformation of binaural information in the dorsal nucleus of the lateral lemniscus (DNLL), a nucleus that connects the binaural nuclei in the brainstem and the inferior colliculus in the midbrain. We used in vitro and in vivo electrophysiology in adult Mongolian gerbils to show that NMDARs play a critical role in neuronal encoding of stimulus properties in the DNLL...
February 6, 2018: European Journal of Neuroscience
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