Maternal immune activation (MIA) during pregnancy leads to long-lasting effects on brain development and function. Several lines of evidence suggest that the maternal inflammatory cytokine interleukin (IL)-6 plays a crucial role in the long-lasting effects of MIA on adult offspring. IL-6 is naturally produced during pregnancy in the absence of any underlying immune activation. The objective of this study was to assess whether this naturally occurring IL-6 has long-lasting effects on brain plasticity and function. Therefore, pregnant rats were given either an IL-6-neutralizing antibody (IL-6Ab) or vehicle during the third week of pregnancy. Newly born (doublecortin) and mature neurons (NeuN) were monitored in the hippocampus of adult male and female offspring. Prenatal IL-6Ab led to an enhanced number of newly born and mature neurons in the dentate gyrus of the hippocampus of male but not female adult offspring. This enhanced neurogenesis was associated with an increased propensity in memory acquisition in male offspring. Blunting the naturally occurring IL-6 during pregnancy did not have a significant long-lasting impact on astrocyte cell density (GFAP), or on anxiety-like behavior as assessed with elevated plus maze and open field tests. Taken together, these data suggest that maternal IL-6 contributes, at least in part, to the programming of the brain’s development in a sex-dependent manner.
Dev Neurosci

中文翻译：

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母体白细胞介素 6 以性依赖方式阻碍成年大鼠后代的海马神经发生

怀孕期间的母体免疫激活 (MIA) 会对大脑发育和功能产生长期影响。几条证据表明，母体炎性细胞因子白细胞介素 (IL)-6 在 MIA 对成年后代的长期影响中起着至关重要的作用。IL-6 在怀孕期间自然产生，没有任何潜在的免疫激活。本研究的目的是评估这种天然存在的 IL-6 是否对大脑可塑性和功能具有长期影响。因此，妊娠大鼠在妊娠第三周给予 IL-6 中和抗体 (IL-6Ab) 或载体。在成年雄性和雌性后代的海马体中监测新生 (doublecortin) 和成熟神经元 (NeuN)。产前 IL-6Ab 导致雄性成年后代海马齿状回中新生和成熟神经元数量增加，而雌性成年后代则没有。这种增强的神经发生与雄性后代记忆获取倾向的增加有关。在怀孕期间钝化自然产生的 IL-6 对星形胶质细胞密度 (GFAP) 或焦虑样行为没有显着的长期影响，正如通过高架十字迷宫和旷场测试所评估的那样。总之，这些数据表明母体 IL-6 至少部分地以性别依赖的方式对大脑发育的编程做出了贡献。在怀孕期间钝化自然产生的 IL-6 对星形胶质细胞密度 (GFAP) 或焦虑样行为没有显着的长期影响，正如通过高架十字迷宫和旷场测试所评估的那样。总之，这些数据表明母体 IL-6 至少部分地以性别依赖的方式对大脑发育的编程做出了贡献。在怀孕期间钝化自然产生的 IL-6 对星形胶质细胞密度 (GFAP) 或焦虑样行为没有显着的长期影响，正如通过高架十字迷宫和旷场测试所评估的那样。总之，这些数据表明母体 IL-6 至少部分地以性别依赖的方式对大脑发育的编程做出了贡献。
开发神经科学