Intensity matters: brain, behaviour and the epigenome of prenatally stressed rats.

There is a general consensus that prenatal stress alters offspring brain development, however, the details are often inconsistent. Hypothesizing that variation to the level of stress would produce different maternal experiences; this study was designed to examine offspring outcomes following a single prenatal stress paradigm at two different intensities. Pregnant Long Evans rats received mild, high, or no-stress from gestational days 12-16. Offspring underwent early behavioural testing and global methylation patterns were analysed from brain tissue of the frontal cortex and hippocampus. The two different prenatal stress intensities produced significantly different and often, opposite effects in the developing brain. Mild prenatal stress decreased brain weight in both males and females, whereas extreme stress increased female brain weight. Mild prenatal stress slowed development of sensorimotor abilities and decreased locomotion, whereas high prenatal stress also slowed development of sensorimotor learning but increased locomotion. Finally, mild prenatal stress increased global DNA methylation levels in the frontal cortex and hippocampus whereas high prenatal stress was associated with a dramatic decrease. The data from this study provide evidence to support a dose-dependent effect of prenatal stress on multiple aspects of brain development, potentially contributing to long-term outcomes.