Neuroactive steroids in the fetal brain: role in the regulation of behaviour and protection against hypoxia

点击翻译按钮获取中文摘要

The major breakdown products of the steroid hormone, progesterone, form a group of hormones termed neuroactive steroids. These steroids have major effects on the activity of the brain and influence behaviour in adult subjects. Changes in the production of steroids by the steroid producing glands influences neurosteroid levels in the adult brain. This in tern may cause behavioural and mood changes in adults, leading to conditions such as premenstrual stress and postnatal depression. In fetal life, the placenta releases large amounts of these neuroactive steroids and high concentrations of these steroid are found in the fetal circulation. We have shown that these steroids suppress the activity of the fetal brain, suppress arousal and maintain the fetus in a sleep-like state during pregnancy. In this proposal we investigate the hypothesis that cells in the fetal brain modify the neuroactive steroid environment within the brain so as to suppress fetal brain activity further during times of stress and, therefore, protect the brain from damage caused by excessive excitation. These mechanisms may prevent brain injury due to placental insufficiency during pregnancy and asphyxia during birth. The augmentation of these natural processes may form the bases for treatment strategies to provide additional protection for the fetal brain in high-risk pregnancies.