NMDA receptor antibody encephalitis (NMDAR-AE) is characterized by cerebrospinal fluid (CSF)-resident anti-NMDA receptor autoantibodies that cause a wide range of neurological manifestations. Although many symptoms are responsive to immunotherapy, behavioral deficits persist, especially in young patients. However, the underlying mechanisms of these long-lasting impairments are unknown. Here, we used a patient-derived GluN1 -specific monoclonal antibody (mAb) to interrogate the underlying mechanisms of long-lasting sensory-motor impairments. Transient exposure to this mAb led to excess callosal projections in somatosensory cortex and resulted in permanent callosal axon alterations in mice. Importantly, these mice displayed persistent fine movement impairments which were similar to those in NMDAR-AE patients. Notably, the severity of these behavioral deficits was tightly correlated with the severity of callosal axon alterations. At the injection site, the anti-GluN1 autoantibody significantly decreased EPH receptor B2 (EPHB2) expression, a regulator of commissural projections, indicating EPHB2s essential role in this phenotype. Our studies reveal important insights into the cellular and molecular basis for persistent sensory-motor deficits in NMDAR-AE.

中文翻译：

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胼胝体终止缺陷是 NMDA 受体抗体脑炎小鼠模型长期行为缺陷的基础

NMDA 受体抗体脑炎 (NMDAR-AE) 的特征是脑脊液 (CSF) 中存在抗 NMDA 受体自身抗体，可引起广泛的神经系统表现。尽管许多症状对免疫疗法有反应，但行为缺陷仍然存在，尤其是在年轻患者中。然而，这些长期损伤的潜在机制尚不清楚。在这里，我们使用源自患者的 GluN1 特异性单克隆抗体 (mAb) 来研究长期感觉运动损伤的潜在机制。短暂接触该 mAb 会导致体感皮层的胼胝体投射过多，并导致小鼠永久性胼胝体轴突改变。重要的是，这些小鼠表现出与 NMDAR-AE 患者相似的持续精细运动障碍。尤其，这些行为缺陷的严重程度与胼胝体轴突改变的严重程度密切相关。在注射部位，抗 GluN1 自身抗体显着降低了 EPH 受体 B2 (EPHB2) 的表达，EPHB2 是连合投射的调节剂，表明 EPHB2 在该表型中起着重要作用。我们的研究揭示了对 NMDAR-AE 中持续感觉运动缺陷的细胞和分子基础的重要见解。