Akademik Veri Yönetim Sistemi
Acta Neurologica Scandinavica, cilt.2025, sa.1, 2025 (SCI-Expanded, Scopus)
Background: Preliminary evidence suggests that astrocytes might contribute to the disease mechanisms of N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, the precise role of astrocytes in the pathogenesis of encephalitis is poorly understood. Methods: To characterize the impact of NMDAR antibodies on the activity of astrocytes, we isolated and purified serum IgG from three patients with NMDAR encephalitis and three healthy controls. Primary cultured mouse astrocytes and neuron–astrocyte cocultures were incubated with 5 μg patient or control IgG for 12 and 24 h. Cell viability and astrocyte activity were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and calcium (Ca2+) imaging studies (using a vector expressing a genetically encoded indicator under the GFAP promoter), respectively. Supernatant levels of TNF-α, a mediator of astrocyte–neuron interactions, were measured by ELISA. Results: Purified serum IgG from N-methyl-D-aspartate receptor-antibody positive patients (NMDAR-Ab+ IgG) and healthy controls did not alter the viability of isolated astrocytes and cocultures. NMDAR-Ab+ IgG suppressed the duration and amplitude of Ca2+ activity of isolated astrocytes at 12 and/or 24 h, whereas all parameters of Ca2+ activity were enhanced by NMDAR-Ab+ IgG in astrocyte–neuron cocultures at 12 h. TNF-α levels were increased in supernatants of NMDAR-Ab+ IgG–administered astrocyte–neuron cocultures but not isolated astrocytes. Discussion: This study provides the first preliminary evidence on the impact of patient-derived NMDAR-Ab+ IgG on astrocytic activity. Our results imply that the interaction of NMDAR-Abs with neurons and astrocytes creates a positive feedback loop reinforcing the activation of astrocytes. TNF-α might be one of the perpetrators of this loop.