Spulber S, Conti M, DuPont C, Raciti M, Bose R, Onishchenko N, Ceccatelli S
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Transl Psychiatry. 2015 Jul 14;5(7):e603. doi: 10.1038/tp.2015.94.
Growing evidence links adverse prenatal conditions to mood disorders. We investigated the long-term behavioral alterations induced by prenatal exposure to excess glucocorticoids (dexamethasone--DEX). At 12 months, but not earlier, DEX-exposed mice displayed depression-like behavior and impaired hippocampal neurogenesis, not reversible by the antidepressant fluoxetine (FLX). Concomitantly, we observed arrhythmic glucocorticoid secretion and absent circadian oscillations in hippocampal clock gene expression. Analysis of spontaneous activity showed progressive alterations in circadian entrainment preceding depression. Circadian oscillations in clock gene expression (measured by means of quantitative PCR) were also attenuated in skin fibroblasts before the appearance of depression. Interestingly, circadian entrainment is not altered in a model of depression (induced by methylmercury prenatal exposure) that responds to FLX. Altogether, our results suggest that alterations in circadian entrainment of spontaneous activity, and possibly clock gene expression in fibroblasts, may predict the onset of depression and the response to FLX in patients.
越来越多的证据表明，产前不良状况与情绪障碍有关。我们研究了产前暴露于过量糖皮质激素（地塞米松——DEX）所引起的长期行为改变。在12个月时，但不是更早，暴露于DEX的小鼠表现出抑郁样行为且海马神经发生受损，抗抑郁药氟西汀（FLX）无法使其恢复。与此同时，我们观察到糖皮质激素分泌无节律以及海马生物钟基因表达的昼夜节律振荡缺失。对自发活动的分析表明，在抑郁出现之前，昼夜节律的同步化存在渐进性改变。在抑郁出现之前，皮肤成纤维细胞中生物钟基因表达的昼夜节律振荡（通过定量PCR测量）也减弱。有趣的是，在对FLX有反应的抑郁模型（由产前暴露于甲基汞诱导）中，昼夜节律同步化没有改变。总之，我们的结果表明，自发活动的昼夜节律同步化改变，以及可能的成纤维细胞中生物钟基因表达的改变，可能预测抑郁症患者的发病以及对FLX的反应。
