Roque Susana, Oliveira Tiago Gil, Nobrega Claudia, Barreira-Silva Palmira, Nunes-Alves Cláudio, Sousa Nuno, Palha Joana Almeida, Correia-Neves Margarida
Life and Health Sciences Research Institute, School of Health Sciences, University of Minho Braga, Portugal.
Front Behav Neurosci. 2011 Feb 7;5:4. doi: 10.3389/fnbeh.2011.00004. eCollection 2011.
Glucocorticoids, namely dexamethasone, are prescribed during late gestation in pregnancies at risk of originating premature newborns, to promote fetal lung maturation. However, adverse early life events have been reported to induce long-lasting changes in the immune and central nervous systems. The accumulating evidence on bidirectional interactions between both systems in psychiatric disorders like depression, prompted us to further investigate the long-term impact of prenatal dexamethasone administration in depressive-like behavior, the immune system and in the ability to mount an immune response to acute infection. The adult male offspring of pregnant dams treated with dexamethasone present depressive-like behavior concomitant with a decrease in CD8(+) T lymphocytes and an increase in B and CD4(+) regulatory T cells. This is accompanied by lower levels of serum interleukin-6 (IL-6) and IL-10. Despite of these differences, when spleen cells are stimulated, in vitro, with lipopolysaccharide, those from adult rats prenatally treated with dexamethasone display a stronger pro-inflammatory cytokine response. However, this immune system profile does not hamper the ability of rats prenatally treated with dexamethasone to respond to acute infection by Listeria monocytogenes. Of notice, L. monocytogenes infection triggers depressive-like behavior in control animals but does not worsen that already present in dexamethasone-treated animals. In summary, prenatal administration of dexamethasone has long-lasting effects on the immune system and on behavior, which are not further aggravated by acute infection with L. monocytogenes.
糖皮质激素，即地塞米松，在妊娠晚期会被用于有早产风险的孕妇，以促进胎儿肺成熟。然而，据报道，早期生活中的不良事件会在免疫和中枢神经系统中引发持久的变化。关于抑郁症等精神疾病中这两个系统之间双向相互作用的证据不断积累，促使我们进一步研究产前给予地塞米松对抑郁样行为、免疫系统以及对急性感染产生免疫反应能力的长期影响。用皮质醇处理的怀孕母鼠的成年雄性后代表现出抑郁样行为，同时CD8(+) T淋巴细胞减少，B细胞和CD4(+) 调节性T细胞增加。这伴随着血清白细胞介素-6（IL-6）和IL-10水平的降低。尽管存在这些差异，但当用脂多糖在体外刺激脾细胞时，产前用地塞米松处理的成年大鼠的脾细胞会表现出更强的促炎细胞因子反应。然而，这种免疫系统特征并不妨碍产前用地塞米松处理的大鼠对单核细胞增生李斯特菌急性感染的反应能力。值得注意的是，单核细胞增生李斯特菌感染在对照动物中引发抑郁样行为，但不会使已经存在于地塞米松处理动物中的抑郁样行为恶化。总之，产前给予地塞米松对免疫系统和行为有长期影响，单核细胞增生李斯特菌急性感染不会进一步加重这些影响。
