Department of Cell and Neurobiology, Keck School of Medicine, Zilkha Neurogenetic Institute, University of Southern California Los Angeles, CA, USA.
Front Cell Neurosci. 2013 Apr 23;7:47. doi: 10.3389/fncel.2013.00047. eCollection 2013.
In addition to its role in the pathophysiology of numerous psychiatric disorders, increasing evidence points to serotonin (5-HT) as a crucial molecule for the modulation of neurodevelopmental processes. Recent evidence indicates that the placenta is involved in the synthesis of 5-HT from maternally derived tryptophan (TRP). This gives rise to the possibility that genetic and environmental perturbations directly affecting placental TRP metabolism may lead to abnormal brain circuit wiring in the developing embryo, and therefore contribute to the developmental origin of psychiatric disorders. In this review, we discuss how perturbations of the placental TRP metabolic pathway may lead to abnormal brain development and function throughout life. Of particular interest is prenatal exposure to maternal depression and antidepressants, both known to alter fetal development. We review existing evidence on how antidepressants can alter placental physiology in its key function of maintaining fetal homeostasis and have long-term effects on fetal forebrain development.
除了在许多精神疾病的病理生理学中发挥作用外,越来越多的证据表明 5-羟色胺(5-HT)是调节神经发育过程的关键分子。最近的证据表明,胎盘参与了从母体色氨酸(TRP)合成 5-HT 的过程。这就产生了这样一种可能性,即直接影响胎盘 TRP 代谢的遗传和环境干扰可能导致发育中的胚胎大脑回路布线异常,从而导致精神疾病的发育起源。在这篇综述中,我们讨论了胎盘 TRP 代谢途径的干扰如何导致整个生命过程中大脑发育和功能的异常。特别有趣的是,产前暴露于母体抑郁和抗抑郁药都已知会改变胎儿的发育。我们回顾了现有的证据,说明抗抑郁药如何改变胎盘的生理功能,以维持胎儿的体内平衡,并对胎儿前脑的发育产生长期影响。