scholarly journals NMDA-receptor antibodies alter cortical microcircuit dynamics

2017 ◽  
Author(s):  
RE Rosch ◽  
S Wright ◽  
G Cooray ◽  
M Papadopoulou ◽  
S Goyal ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Mouse Model ◽  
Spectral Composition ◽  
Field Potential ◽  
Autoimmune Encephalitis ◽  
Neuronal Population ◽  
Diverse Range ◽  
Excitatory Neurotransmitter ◽  
Eeg Abnormalities ◽  
Receptor Antibodies

AbstractNMDA-receptor antibodies (NMDAR-Ab) cause an autoimmune encephalitis with a diverse range of electroencephalographic (EEG) abnormalities. NMDAR-Ab are believed to disrupt receptor function, but how blocking this excitatory neurotransmitter can lead to paroxysmal EEG abnormalities – or even seizures – is poorly understood. Here, we show that NMDAR-Ab change intrinsic cortical connections and neuronal population dynamics to alter the spectral composition of spontaneous EEG activity, and predispose to paroxysmal EEG abnormalities. Based on local field potential recordings in a mouse model, we first validate a dynamic causal model of NMDAR-Ab effects on cortical microcircuitry. Using this model, we then identify the key synaptic parameters that best explain EEG paroxysms in paediatric patients with NMDAR-Ab encephalitis. Finally, we use the mouse model to show that NMDAR-Ab- related changes render microcircuitry critically susceptible to overt EEG paroxysms, when these key parameters are changed. These findings offer mechanistic insights into circuit-level dysfunction induced by NMDAR-Ab.

scholarly journals NMDA-receptor antibodies alter cortical microcircuit dynamics

2018 ◽  
Vol 115 (42) ◽  
pp. E9916-E9925 ◽  
Author(s):  
Richard E. Rosch ◽  
Sukhvir Wright ◽  
Gerald Cooray ◽  
Margarita Papadopoulou ◽  
Sushma Goyal ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Mouse Model ◽  
Spectral Composition ◽  
Field Potential ◽  
Autoimmune Encephalitis ◽  
Neuronal Population ◽  
Diverse Range ◽  
Eeg Abnormalities ◽  
Synaptic Parameters ◽  
Receptor Antibodies

NMDA-receptor antibodies (NMDAR-Abs) cause an autoimmune encephalitis with a diverse range of EEG abnormalities. NMDAR-Abs are believed to disrupt receptor function, but how blocking this excitatory synaptic receptor can lead to paroxysmal EEG abnormalities—or even seizures—is poorly understood. Here we show that NMDAR-Abs change intrinsic cortical connections and neuronal population dynamics to alter the spectral composition of spontaneous EEG activity and predispose brain dynamics to paroxysmal abnormalities. Based on local field potential recordings in a mouse model, we first validate a dynamic causal model of NMDAR-Ab effects on cortical microcircuitry. Using this model, we then identify the key synaptic parameters that best explain EEG paroxysms in pediatric patients with NMDAR-Ab encephalitis. Finally, we use the mouse model to show that NMDAR-Ab–related changes render microcircuitry critically susceptible to overt EEG paroxysms when these key parameters are changed, even though the same parameter fluctuations are tolerated in the in silico model of the control condition. These findings offer mechanistic insights into circuit-level dysfunction induced by NMDAR-Ab.

scholarly journals Anti-N-Methyl-D-Aspartate Encephalitis as Paraneoplastic Manifestation of Germ-Cells Tumours: A Cases Report and Literature Review

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Claudia Geraldine Rita ◽  
Israel Nieto Gañan ◽  
Adriano Jimenez Escrig ◽  
Ángela Carrasco Sayalero
Keyword(s):  
Nmda Receptor ◽  
Germ Cell ◽  
Germ Cells ◽  
Germ Cell Tumour ◽  
Clinical Manifestations ◽  
Autoimmune Encephalitis ◽  
Cell Tumour ◽  
Ovarian Teratoma ◽  
Surgical Removal ◽  
Receptor Antibodies

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is the most common form of autoimmune encephalitis, caused by the interaction between an antibody and its target, located on glutamate receptor type N-methyl-D-aspartate (NMDA) of neuronal surface. There is a wide spectrum of clinical features starting by a viral-like prodrome, followed by symptoms such as psychosis, aggressive behaviour, memory loss, seizures, movement disorders, and autonomic instability. Up to 50% of the affected young female patients have germ-cells tumours as ovarian teratoma, making it essential to establish an early diagnosis through detection of specific antibodies in serum and cerebrospinal fluid (CSF). This retrospective observational study was performed in patients whom positive anti-NMDA receptor antibodies have been tested, associated with clinical manifestations that suggest autoimmune encephalitis and a germ-cell tumour confirmed by pathology. Six patients have tested positive for anti-NMDA receptor antibodies associated with a germ-cell tumour and clinical manifestations of autoimmune encephalitis. Management includes aggressive immunosuppression and surgical removal.

Malignant tumors in autoimmune encephalitis with anti-NMDA receptor antibodies

2018 ◽  
Vol 265 (10) ◽  
pp. 2190-2200 ◽  
Author(s):  
Chloé Bost ◽  
Eve Chanson ◽  
Géraldine Picard ◽  
David Meyronet ◽  
Marie-Eve Mayeur ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Malignant Tumors ◽  
Autoimmune Encephalitis ◽  
Receptor Antibodies

scholarly journals Atypical Association of Autoimmune Limbic Encephalitis with Anti-NMDA Receptor Antibodies in a Young Male Patient: Clinical, Imaging, and Neuropsychological Characteristics

2021 ◽  
pp. 541-548
Author(s):  
José Alberto Choreño-Parra ◽  
Tania de la Rosa-Arredondo ◽  
André Garibay-Gracián ◽  
Ingrid Montes de Oca-Vargas ◽  
Deyanira Capi-Casillas ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Limbic Encephalitis ◽  
Psychiatric Symptoms ◽  
Brain Mri ◽  
Clinical Manifestations ◽  
Memory Loss ◽  
Autoimmune Encephalitis ◽  
Young Male ◽  
Autoimmune Limbic Encephalitis ◽  
Receptor Antibodies

The spectrum of autoimmune encephalitis (AE) encompasses several entities characterized by a variable frequency of psychiatric symptoms, cognitive dysfunction, focal deficits, and seizures. Although patients with AE can be categorized in specific syndromes, overlapping manifestations are also common. Furthermore, atypical correlations between clinical phenotypes and autoantibody profiles could occur in rare cases. Here, we report the rare case of a young adult man attending due to new-onset seizures and a history of memory loss, autonomic disturbances, headache, behavioral changes, and visual and olfactory hallucinations. The patient was subjected to a complete diagnostic approach that included a comprehensive laboratory workup, neuropsychological testing, electroencephalogram, cerebrospinal fluid (CSF) analysis, brain MRI, and positron emission tomography/computed tomography scan that revealed a functional and structural compromise of the bilateral medial temporal lobes. Together with the clinical manifestations of the patient, these findings were compatible with the diagnosis of autoimmune limbic encephalitis (ALE). Strikingly, further analysis of the CSF showed autoantibodies against the N-methyl-D-aspartate (NMDA) receptor. We found very few cases of the co-occurrence of anti-NMDA receptor antibodies and nonparaneoplastic ALE in the literature, especially in male patients. Our report exemplifies the complicated differential diagnosis of ALE and adds clinical information of the association with anti-NMDA receptor antibodies.

scholarly journals Solitary juxtacortical lesion associated with anti-N-methyl-D-aspartate receptor encephalitis: a case report

BMC Neurology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Rupan Gao ◽  
Xiang Zhang ◽  
Abhijeet Kumar Bhekharee ◽  
Yue Zhang
Keyword(s):  
Nmda Receptor ◽  
Frontal Lobe ◽  
Brain Mri ◽  
Brain Lesion ◽  
Autoimmune Encephalitis ◽  
Left Frontal Lobe ◽  
Solitary Lesion ◽  
Nmda Receptor Encephalitis ◽  
Epileptiform Discharges ◽  
Receptor Antibodies

Abstract Background Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a severe autoimmune encephalitis mediated by anti-NMDA receptor antibodies. Brain MRI manifestations vary and are non-specific. If there are any lesions, they tend to be diffusely or multifocally distributed. Solitary lesion is relatively rare. Case presentation We report a 16-year-old girl who initially presented with focal seizures but developed severe psychiatric and extrapyramidal symptoms later on. Brain MRI revealed a solitary juxtacortical demyelinating lesion in the left frontal lobe. No enhancement was noted. Electroencephalogram captured epileptiform discharges in the same region. NMDAR IgGs were tested positive in the serum and cerebrospinal fluid. Corticosteroid and intravenous IgG were administered and the patient completely recovered. Brain MRI revealed a fainter lesion in the left frontal lobe. Conclusion In very rare instances, anti-NMDA receptor encephalitis can present with a solitary brain lesion. A full panel of antibodies for autoimmune encephalitis is the key leading to the diagnosis.

New-Onset Headache in Patients With Autoimmune Encephalitis Is Associated With anti-NMDA-Receptor Antibodies

2016 ◽  
Vol 56 (6) ◽  
pp. 995-1003 ◽  
Author(s):  
Christoph J. Schankin ◽  
Fabian Kästele ◽  
Lisa Ann Gerdes ◽  
Tobias Winkler ◽  
Endy Csanadi ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Autoimmune Encephalitis ◽  
Receptor Antibodies ◽  
New Onset

Imaging NMDA- and kainate-induced intrinsic optical signals from the hippocampal slice

1996 ◽  
Vol 76 (4) ◽  
pp. 2707-2717 ◽  
Author(s):  
R. D. Andrew ◽  
J. R. Adams ◽  
T. M. Polischuk
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Ampa Receptors ◽  
Hippocampal Slice ◽  
Field Potential ◽  
Nmda Receptor Antagonist ◽  
Light Transmittance ◽  
Stratum Radiatum ◽  
Cell Swelling ◽  
Tissue Resistance

1. Brain ischemia causes excess release and accumulation of glutamate that binds to postsynaptic receptors. This opens ionotropic channels that mediate neuronal depolarization and ionic fluxes that can lead to neuronal death. 2. The CA1 pyramidal cell region of the hippocampus is particularly susceptible to this neurotoxic process. Brain cell swelling is considered an early excitotoxic event, but remains poorly under stood and documented. As cells swell, light transmittance (LT) increases through brain tissue, so we hypothesized that brief exposure to glutamate agonists would elicit cell swelling that could be imaged in real time in the hippocampal slice. 3. A 1-min bath application of 100 microM N-methyl-D-aspartate (NMDA) or 100 microM kainate at 22 degrees C greatly increased LT, particularly in the dendritic regions of CA1. The response peaked by 2-3 min and slowly reversed over the subsequent 20 min following exposure. Peak LT increases were > 50% in CA1 stratum radiatum and > 20% in both CA1 stratum oriens and the dendritic region of the dentate gyrus, all areas with a high concentration of NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors. The CA3 stratum radiatum, which contains fewer of these receptors, showed a comparatively small LT increase. 4. The NMDA receptor antagonist 2-amino-5-phosphonovalerate (AP-5) [but not 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)] blocked the CA1 response to NMDA, whereas the non-NMDA receptor antagonist CNQX (but not AP-5) blocked the response to kainate. The relative tissue resistance measured across CA1 stratum radiatum increased after NMDA or kainate exposure with a time course similar to the LT change described above. The increase in relative tissue resistance was blocked by kynurenate, a nonspecific glutamate antagonist. Increases in both LT and tissue resistance provide two independent lines of evidence that cell swelling rapidly developed in CA1 dendritic areas after activation of NMDA or AMPA receptors. 5. This swelling at 22 degrees C was accompanied by a temporary loss of the evoked CA1 field potential. However, at 37 degrees C the dendritic swelling rapidly progressed to an irreversible LT increase (swelling) of the CA1 cell bodies accompanied by a permanent loss of the evoked field. 6. We propose that dendritic swelling mediated by NMDA and AMPA receptors is an early excitotoxic event that can herald permanent damage to CA1 neurons, those cells most vulnerable to ischemic insult.

Ferulic acid through mitigation of NMDA receptor pathway exerts anxiolytic-like effect in mouse model of maternal separation stress

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Zahra Lorigooini ◽  
Ali Nouri ◽  
Faezeh mottaghinia ◽  
Shima Balali-Dehkordi ◽  
Elham Bijad ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Mouse Model ◽  
Ferulic Acid ◽  
Nmda Receptors ◽  
Effective Dose ◽  
Life Stress ◽  
Receptor Agonist ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Central Zone

AbstractBackgroundExperiencing early-life stress plays an important role in the pathophysiology of anxiety disorders. Ferulic acid is a phenolic compound found in some plants which has several pharmacological properties. N-methyl-D-aspartate (NMDA) receptors are involved in the pathophysiology of mood disorders. In this study we aimed to assess the anxiolytic-like effect of ferulic acid in a mouse model of maternal separation (MS) stress by focusing on the possible involvement of NMDA receptors.MethodsMice were treated with ferulic acid (5 and 40 mg/kg) alone and in combination with NMDA receptor agonist/antagonist. Valid behavioral tests were performed, including open field test (OFT) and elevated plus maze test (EPM), while quantitative real time polymerase chain reaction (qRT-PCR) was used to evaluate gene expression of NMDA subunits (GluN2A and GluN2B) in the hippocampus.ResultsFindings showed that treatment of MS mice with ferulic acid increased the time spent in the central zone of the OFT and increased both open arm time and the percent of open arm entries in the EPM. Ferulic acid reduced the expression of NMDA receptor subunit genes. We showed that administration of NMDA receptor agonist (NMDA) and antagonist (ketamine) exerted anxiogenic and anxiolytic-like effects, correspondingly. Results showed that co-administration of a sub-effective dose of ferulic acid plus ketamine potentiated the anxiolytic-like effect of ferulic acid. Furthermore, co-administration of an effective dose of ferulic acid plus NMDA receptor agonist (NMDA) attenuated the anxiolytic-like effect of ferulic acid.ConclusionsIn deduction, our findings showed that NMDA, partially at least, is involved in the anxiolytic-like effect of ferulic acid in the OFT and EPM tests.

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