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<p>Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis (NMDARE) is an autoimmune neurological disorder associated with anti-NMDAR antibodies (NMDAR-Ab), leading to synaptic dysfunction. While the effect of NMDAR-Ab on receptor internalization is well documented, its effect on dendritic protrusion morphology remains unclear. To investigate how NMDAR-Ab alters dendritic protrusion size and the associated molecular mechanisms using patient-derived sera. Cultured hippocampal neurons were treated with sera from patients with NMDARE. Protrusion size and the phosphorylation of cofilin, a regulator of actin dynamics, were also assessed. Exposure to NMDAR-Ab significantly decreased dendritic protrusion width and length while increasing protrusion density. Mechanistically, NMDAR-Ab decreased cofilin phosphorylation in dendritic protrusions. The reduction in spine size was partially reversible upon discontinuation of antibody treatment, except for the reduction in phosphorylated cofilin levels. NMDAR-Ab induced changes in dendritic protrusion size, along with alterations in actin dynamics, which may contribute to the cognitive and behavioral symptoms of NMDARE.</p>

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Pathogenic human autoantibodies against NMDA receptor alter dendritic spine size

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月3日

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  • Shimpei Matsuda,
  • Takayuki Mori,
  • Mariko Kasai,
  • Kuniko Kohyama,
  • Tadayuki Shimada,
  • Hiroshi Sakuma

摘要

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis (NMDARE) is an autoimmune neurological disorder associated with anti-NMDAR antibodies (NMDAR-Ab), leading to synaptic dysfunction. While the effect of NMDAR-Ab on receptor internalization is well documented, its effect on dendritic protrusion morphology remains unclear. To investigate how NMDAR-Ab alters dendritic protrusion size and the associated molecular mechanisms using patient-derived sera. Cultured hippocampal neurons were treated with sera from patients with NMDARE. Protrusion size and the phosphorylation of cofilin, a regulator of actin dynamics, were also assessed. Exposure to NMDAR-Ab significantly decreased dendritic protrusion width and length while increasing protrusion density. Mechanistically, NMDAR-Ab decreased cofilin phosphorylation in dendritic protrusions. The reduction in spine size was partially reversible upon discontinuation of antibody treatment, except for the reduction in phosphorylated cofilin levels. NMDAR-Ab induced changes in dendritic protrusion size, along with alterations in actin dynamics, which may contribute to the cognitive and behavioral symptoms of NMDARE.