BioProject

Some neuropsychiatric disease, including schizophrenia, may originate during prenatal development, following periods of gestational hypoxia and placental oxidative stress. More...

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. Overall design: Total RNA extracted from rat foetal E20 plasma or culture medium conditioned by rat placenta was analysed for microRNA content. Samples were derived from 4 different in vivo conditions (maternal normoxia+saline injection = Control, maternal hypoxia+saline injection, maternal normoxia+MitoQ-NP injections, maternal hypoxia+MitoQ-NP injection). For placenta-conditioned media, samples underwent furher in vitro conditions (expsoure to 21% oxygen, exposure to 2% oxygen, expsosure to 8% oxygen). 4 biological replicates were measured per condition, except for maternal hypoxia+saline injection (foetal plasma), maternal normoxia+saline injection+2%oxygen (placenta-conditioned media) and all placenta-conditioned media samples exposed to 8% oxygen, for which 3 replicates were measured. Less...