Chang Eric H, Volpe Bruce T, Mackay Meggan, Aranow Cynthia, Watson Philip, Kowal Czeslawa, Storbeck Justin, Mattis Paul, Berlin RoseAnn, Chen Huiyi, Mader Simone, Huerta Tomás S, Huerta Patricio T, Diamond Betty
Laboratory of Immune & Neural Networks, Feinstein Institute for Medical Research, North Shore LIJ Health System, Manhasset, NY 11030, USA.
Laboratory of Functional Neuroanatomy, Feinstein Institute for Medical Research, North Shore LIJ Health System, Manhasset, NY 11030, USA ; Department of Molecular Medicine, Hofstra North Shore-LIJ School of Medicine, Manhasset, NY 11030, USA.
EBioMedicine. 2015 May 30;2(7):755-64. doi: 10.1016/j.ebiom.2015.05.027. eCollection 2015 Jul.
Patients with systemic lupus erythematosus (SLE) experience cognitive abnormalities in multiple domains including processing speed, executive function, and memory. Here we show that SLE patients carrying antibodies that bind DNA and the GluN2A and GluN2B subunits of the N-methyl-d-aspartate receptor (NMDAR), termed DNRAbs, displayed a selective impairment in spatial recall. Neural recordings in a mouse model of SLE, in which circulating DNRAbs penetrate the hippocampus, revealed that CA1 place cells exhibited a significant expansion in place field size. Structural analysis showed that hippocampal pyramidal cells had substantial reductions in their dendritic processes and spines. Strikingly, these abnormalities became evident at a time when DNRAbs were no longer detectable in the hippocampus. These results suggest that antibody-mediated neurocognitive impairments may be highly specific, and that spatial cognition may be particularly vulnerable to DNRAb-mediated structural and functional injury to hippocampal cells that evolves after the triggering insult is no longer present.
系统性红斑狼疮（SLE）患者在多个认知领域存在异常，包括处理速度、执行功能和记忆。我们在此表明，携带与DNA以及N-甲基-D-天冬氨酸受体（NMDAR）的GluN2A和GluN2B亚基结合的抗体（称为DNRAbs）的SLE患者在空间记忆方面存在选择性损伤。在SLE小鼠模型中进行的神经记录显示，循环中的DNRAbs穿透海马体，CA1区位置细胞的位置野大小显著扩大。结构分析表明，海马锥体细胞的树突分支和棘突大量减少。令人惊讶的是，当在海马体中不再能检测到DNRAbs时，这些异常变得明显。这些结果表明，抗体介导的神经认知障碍可能具有高度特异性，并且空间认知可能特别容易受到DNRAb介导的对海马细胞的结构和功能损伤的影响，这种损伤在引发损伤不再存在后仍会发展。
