TY -的T1 -从行为到突触:被动转移的小鼠模型Anti-NMDAR脑炎患者的抗体(S63.007) JF -神经学乔-神经学六世- 82 - 10补充SP - S63.007盟Mannara Francesco AU -哈维尔·古铁雷斯单面山AU -弗兰克Leypoldt AU -耶稣Pla首页naguma AU -埃琳娜·马丁·加西亚盟Ankit Jain AU -弗朗西斯克格劳盟丽塔Balice-Gordon AU -拉斐尔Maldonado洛佩兹盟约瑟Dalmau Y1 - 2014/04/08 UR - //www.ez-admanager.com/content/82/10_Supplement/S63.007.abstract N2 -目的:报告动物模型的记忆和行为从Anti-NMDAR脑炎患者赤字引起的抗体。背景:anti-NMDAR脑炎患者发展突出的行为和记忆缺陷。我们之前显示病人的抗体引起特定的密度减少,突触本地化和NMDARs功能神经元和老鼠大脑的文化。然而,抗体介入的确认发病机理取决于建模在动物身上的症状。方法:C57 / BL6小鼠接受输液病人的通过脑室导管连接皮下注射或控制脑脊液渗透泵(连续注入0.5µl 14天/小时)。内存(V-maze对象识别),焦虑(高架加上迷宫),侵略(居民入侵者)、快感缺乏(食用蔗糖)、抑郁(尾部),和运动活动评估盲目地在5天,13日,18日和26日。代表动物的大脑获得在每个时间点检测抗体绑定和影响NMDAR使用定量免疫印迹和共焦显微镜。结果:18小鼠注射患者的CSF和20控制包括在这项研究中。与控制相比,最戏剧性的影响是逐步减少在天的记忆抗体注入(10天:NMDAR 0.41±0.06, 0.35±0.05与控制术;0.001),18天达到最大效应(NMDAR 0.46±0.05, 0.15±0.04与控制 p<0.001), and normalizing on day 25 (NMDAR 0,47±0,02 versus control 0.50±0.03; p>0.05). In addition, animals injected with patients’ CSF had more depressed behavior (NMDAR 187.00s±7.07 versus control 153.30s±9.76; p=0.006) and anhedonia (NMDAR 76.64±6.37 versus control 87.66±0.79; p=0.068). Brain studies showed that animals injected with patients’ CSF, but not control CSF, had NMDAR antibodies bound to hippocampus, along with a reversible decrease of the levels and synaptic localization of NMDAR (p=0.018). CONCLUSIONS: Antibodies from patients with anti-NMDAR encephalitis cause memory and behavioral deficits related to antibody-mediated decrease of hippocampal NMDAR. Study Supported by: Instituto Carlos III, FIS PI11/01780 (JD) and PI112/00611 (FG), and the NIH RO1NS077851 (JD), MH094741 (RB-G and JD)and Fundació la Marató TV3 (101530 JD)Disclosure: Dr. Francesco has nothing to disclose. Dr. Gutierrez Cuesta has nothing to disclose. Dr. Leypoldt has received personal compensation for activities with Grifols as a speaker. Dr. Planagumà has nothing to disclose. Dr. Martín García has nothing to disclose. Dr. Jain has nothing to disclose. Dr. Graus has nothing to disclose. Dr. Balice-Gordon has received personal compensation for activities with Pfizer, Inc. as an employee. Dr. Maldonado Lopez has nothing to disclose. Dr. Dalmau has received personal compensation in an editorial capacity for Up To Date. Dr. Dalmau has received royalty payments from Athena Diagnostics. Dr. Dalmau has received research support from Euroimmun.Thursday, May 1 2014, 3:15 pm-5:00 pm ER -