دورية أكاديمية
Human N-Methyl-D-aspartate receptor antibodies alter memory and behavior in mice
| العنوان: | Human N-Methyl-D-aspartate receptor antibodies alter memory and behavior in mice |
|---|---|
| المؤلفون: | Planagumà, Jesús, Leypoldt, Frank, Mannara, Francesco, Gutiérrez-Cuesta, Javier, Martín-García, Elena, Aguilar, Esther, Titulaer, Maarten J., Jain, Ankit, Balice-Gordon, Rita, Lakadamyali, Melike, Graus, Francesc, Maldonado, Rafael, Dalmau, Josep |
| المساهمون: | Universitat Politècnica de Catalunya. Institut de Ciències Fotòniques |
| بيانات النشر: | Oxford |
| سنة النشر: | 2015 |
| المجموعة: | Universitat Politècnica de Catalunya (UPC): Tesis Doctorals en Xarxa (TDX) / Theses and Dissertations Online |
| مصطلحات موضوعية: | Àrees temàtiques de la UPC::Física, Antibodies, Animal model, Anticossos |
| الوصف: | Anti-N-methyl D-aspartate receptor (NMDAR) encephalitis is a severe neuropsychiatric disorder that associates with prominent memory and behavioural deficits. Patients’ antibodies react with the N-terminal domain of the GluN1 (previously known as NR1) subunit of NMDAR causing in cultured neurons a selective and reversible internalization of cell-surface receptors. These effects and the frequent response to immunotherapy have suggested an antibody-mediated pathogenesis, but to date there is no animal model showing that patients’ antibodies cause memory and behavioural deficits. To develop such a model, C57BL6/J mice underwent placement of ventricular catheters connected to osmotic pumps that delivered a continuous infusion of patients’ or control cerebrospinal fluid (flow rate 0.25 µl/h, 14 days). During and after the infusion period standardized tests were applied, including tasks to assess memory (novel object recognition in open field and V-maze paradigms), anhedonic behaviours (sucrose preference test), depressive-like behaviours (tail suspension, forced swimming tests), anxiety (black and white, elevated plus maze tests), aggressiveness (resident-intruder test), and locomotor activity (horizontal and vertical). Animals sacrificed at Days 5, 13, 18, 26 and 46 were examined for brain-bound antibodies and the antibody effects on total and synaptic NMDAR clusters and protein concentration using confocal microscopy and immunoblot analysis. These experiments showed that animals infused with patients’ cerebrospinal fluid, but not control cerebrospinal fluid, developed progressive memory deficits, and anhedonic and depressive-like behaviours, without affecting other behavioural or locomotor tasks. Memory deficits gradually worsened until Day 18 (4 days after the infusion stopped) and all symptoms resolved over the next week. Accompanying brain tissue studies showed progressive increase of brain-bound human antibodies, predominantly in the hippocampus (maximal on Days 13–18), that after acid extraction and ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 16 p. |
| اللغة: | English |
| العلاقة: | http://doi.org/10.1093/brain/awu310Test; info:eu-repo/grantAgreement/EC/FP7/337191/EU/On the move: Motor-cargo and motor-microtubule interactions studied with quantitative, high spatio-temporal resolution microscopy in vivo/MOTORS; http://hdl.handle.net/2117/88911Test |
| الإتاحة: | https://doi.org/10.1093/brain/awu310Test http://hdl.handle.net/2117/88911Test |
| حقوق: | Attribution-NonCommercial-NoDerivs 3.0 Spain ; http://creativecommons.org/licenses/by-nc-nd/3.0/esTest/ ; Open Access |
| رقم الانضمام: | edsbas.8212923 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |