School of Clinical Sciences, University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK.
Department of Obstetrics and Gynecology and Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada.
Sci Rep. 2017 Aug 22;7(1):9079. doi: 10.1038/s41598-017-06300-1.
Some neuropsychiatric disease, including schizophrenia, may originate during prenatal development, following periods of gestational hypoxia and placental oxidative stress. Here we investigated if gestational hypoxia promotes damaging secretions from the placenta that affect fetal development and whether a mitochondria-targeted antioxidant MitoQ might prevent this. Gestational hypoxia caused low birth-weight and changes in young adult offspring brain, mimicking those in human neuropsychiatric disease. Exposure of cultured neurons to fetal plasma or to secretions from the placenta or from model trophoblast barriers that had been exposed to altered oxygenation caused similar morphological changes. The secretions and plasma contained altered microRNAs whose targets were linked with changes in gene expression in the fetal brain and with human schizophrenia loci. Molecular and morphological changes in vivo and in vitro were prevented by a single dose of MitoQ bound to nanoparticles, which were shown to localise and prevent oxidative stress in the placenta but not in the fetus. We suggest the possibility of developing preventative treatments that target the placenta and not the fetus to reduce risk of psychiatric disease in later life.
一些神经精神疾病，包括精神分裂症，可能起源于产前发育，在妊娠期缺氧和胎盘氧化应激之后。在这里，我们研究了妊娠期缺氧是否会促进胎盘产生有害分泌物质，从而影响胎儿发育，以及一种靶向线粒体的抗氧化剂 MitoQ 是否可以预防这种情况。妊娠期缺氧导致低出生体重和年轻成年后代大脑的变化，类似于人类神经精神疾病的情况。将培养的神经元暴露于胎儿血浆或胎盘分泌物中，或暴露于已改变氧合的模型滋养层屏障中，会导致类似的形态变化。这些分泌物和血浆中含有改变的 microRNA，其靶标与胎儿大脑中的基因表达变化以及人类精神分裂症基因座相关。体内和体外的分子和形态变化可通过与纳米颗粒结合的单次剂量 MitoQ 来预防，该纳米颗粒被证明可在胎盘而非胎儿中定位并预防氧化应激。我们提出了一种可能性，即开发针对胎盘而不是胎儿的预防治疗方法，以降低日后患精神疾病的风险。
