Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Psychopharmacology (Berl). 2022 Feb;239(2):525-531. doi: 10.1007/s00213-021-06036-x. Epub 2021 Dec 2.
Adequate immunotherapies for anti-NMDAR encephalitis during pregnancy produce a relatively good clinical outcome for pregnant mothers and their infants, but there are no reports about the future growth of their babies. The damage of anti-NMDAR antibodies to early neuronal development is still unknown.
Serum or cerebrospinal fluid from one patient with anti-NMDAR encephalitis (the index patient) and one patient with schizophrenia (the control patient) was administered to primary cultures of dissociated rat cortical neurons, and dendritic outgrowth, centrosome elimination, and branching of dendrites were investigated. For rescue experiments, serum of the index patient was replaced with normal culture media after 3 days' administration of the index patient.
Serum and cerebrospinal fluid of the index patient statistically significantly impaired dendritic outgrowth of cultured rat cortical primary neurons. Serum of the index patient also statistically significantly delayed centrosome elimination. Impaired dendritic outgrowth and delayed centrosome elimination were not perfectly rescued by changing to normal culture media. Serum of the index patient also statistically significantly reduced the branching of dendrites.
This is the first demonstration of the damage by anti-NMDAR antibodies on early dendritic development in vitro. As a strategy to protect embryonic neurons, our findings may support the efficacy of early immunotherapy for anti-NMDAR encephalitis in pregnancy.
在妊娠期间使用适当的免疫疗法治疗抗 NMDAR 脑炎,可使孕妇及其婴儿获得较好的临床结局,但目前尚无关于其婴儿未来生长发育的报道。抗 NMDAR 抗体对早期神经元发育的损害仍不清楚。
将一名抗 NMDAR 脑炎患者(指标患者)和一名精神分裂症患者(对照患者)的血清或脑脊液分别作用于原代培养的大鼠皮质神经元,观察树突生长、中心体消除和树突分支的情况。在挽救实验中,在给予指标患者血清 3 天后,用正常培养基替换指标患者的血清。
指标患者的血清和脑脊液可显著抑制培养的大鼠皮质原代神经元的树突生长。指标患者的血清也可显著延迟中心体消除。用正常培养基替换并不能完全挽救受损的树突生长和延迟的中心体消除。指标患者的血清还可显著减少树突分支。
这是首次在体外证明抗 NMDAR 抗体对早期树突发育的损害。作为保护胚胎神经元的一种策略,我们的发现可能支持妊娠期间早期免疫治疗抗 NMDAR 脑炎的疗效。