MATERNAL STRESS IMPAIRS FETAL DEVELOPMENT AND LEARNING AND MEMORY IN ADULT OFFSPRING MICE

초록

The present study examines whether chronic stress to pregnant mice affects fetal limb development. ICR pregnant mice were placed individually in a plastic cylinder for 6 hrs (from 10:00a.m. to 4:00p.m.) a day from 8.5 gestation day until sacrifice. Our protocol increased sustained stress hormones such as corticosterone and catecholamines. Maternal stress increased abortion rate up to 30%, decreased fetal and neonatal body weight and retarded fetal limb development about 1 day in E14.5 fetal stage. To examine whether maternal stress influences the synaptic function of hippocampus of adult offspring, the newborn mice born from stressed mother were reared under normal environment until six weeks (adult offspring) and electrophysiological parameters were measured using the hippocampal brain slices: There were no significant differences between normal and stressed adult offspring in the extent of paired pulse facilitation (PPF), a presynaptic form of the short-term plasticity. However, long-term potentiation (LTP) in the hippocampal CA1 area derived from stressed offsprings was significantly decreased compared to that of normal mice. In accordance with decreased LTP, spatial learning ability and even simple learning capacity were impaired in the stressed adult offspring, determined with Morris water maze training and passive fear avoidance training, respectively. Taken together, these data evidently suggest that pre-natal stress leads to developmental and physiological perturbations. The hippocampal synaptic strength and learning and memory functions were significantly reduced even when offsprings were reared and became adults in a normal environment.