Chronic presence of blood circulating anti-NMDAR1 autoantibodies impairs cognitive function in mice.
Chronic presence of blood circulating anti-NMDAR1 autoantibodies impairs cognitive function in mice.
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DOI：
10.1371/journal.pone.0256972
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Zhou X
中科院分区：
文献类型：
--
作者：
Yue W;Caldwell S;Risbrough V;Powell S;Zhou X
脑中高滴度的抗NMDAR 1自身抗体引起抗NMDAR 1脑炎，其显示精神分裂症的精神症状和/或除神经症状之外的其他精神障碍。在一般人群和精神病患者的血液中报告了低滴度的抗NMDAR 1自身抗体。由于约0.1-0.2%的血液循环抗体穿过血脑屏障，并且抗体可以在人血液中持续数月和数年，因此研究这些血液循环抗NMDAR 1自身抗体的长期存在是否会损害人类认知功能并导致精神症状的发展是重要的。在这里，我们产生了在血液中携带针对小鼠NMDAR 1的单个抗原表位的低滴度抗NMDAR 1自身抗体的小鼠。携带抗NMDAR 1自身抗体的小鼠是健康的，与对照组相比，在运动、感觉运动门控和背景记忆方面没有差异。然而，血液循环抗NMDAR 1自身抗体的长期存在足以损害所有3个独立小鼠组群中血脑屏障完整性的T-迷宫自发交替，表明空间工作记忆和/或新奇检测中的稳健认知缺陷。我们的研究表明，长期存在的低滴度的血液循环抗NMDAR 1自身抗体可能会损害一般健康人群和精神病患者的认知功能。
High titers of anti-NMDAR1 autoantibodies in brain cause anti-NMDAR1 encephalitis that displays psychiatric symptoms of schizophrenia and/or other psychiatric disorders in addition to neurological symptoms. Low titers of anti-NMDAR1 autoantibodies are reported in the blood of a subset of the general human population and psychiatric patients. Since ~0.1–0.2% of blood circulating antibodies cross the blood-brain barriers and antibodies can persist for months and years in human blood, it is important to investigate whether chronic presence of these blood circulating anti-NMDAR1 autoantibodies may impair human cognitive functions and contribute to the development of psychiatric symptoms. Here, we generated mice carrying low titers of anti-NMDAR1 autoantibodies in blood against a single antigenic epitope of mouse NMDAR1. Mice carrying the anti-NMDAR1 autoantibodies are healthy and display no differences in locomotion, sensorimotor gating, and contextual memory compared to controls. Chronic presence of the blood circulating anti-NMDAR1 autoantibodies, however, is sufficient to impair T-maze spontaneous alternation in the integrity of blood-brain barriers across all 3 independent mouse cohorts, indicating a robust cognitive deficit in spatial working memory and/or novelty detection. Our studies implicate that chronic presence of low titers of blood circulating anti-NMDAR1 autoantibodies may impair cognitive functions in both the general healthy human population and psychiatric patients.
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