Delayed effects of early stress on hippocampal development.

Early maternal separation has been shown in animal models to produce enduring morphological changes in the hippocampus and other brain structures, which may not become evident until adulthood. Postnatally, the trajectory of overproduction and pruning of axons, dendrites, synapses and receptors shapes the brain between puberty and adulthood. The objective of the study was to ascertain whether this normal trajectory was affected by repeated maternal separation. Rat pups were separated from their mother for 4 h a day between postnatal days 2 and 20 (ISO group), and compared to rat pups that remained with their mother in the animal facilities (AFR group) and were exposed to minimal handling. Immunoreactivity to synaptophysin was quantified in the hippocampus CA1 and CA3, amygdala, and prefrontal cortex using optical densitometry (OD) at 25, 40, 60, 80, and 100 days in male and female rats. Synaptophysin OD increased dramatically in CA1 and CA3 between 25 and 60 days in the AFR group and fell by the same degree between 60 and 100 days, showing the expected sequence of overproduction and pruning. No difference between groups in synaptophysin OD was observed at 25 and 40 days. However, at day 60 synaptophysin was 34-36% lower in CA1 and CA3 of the ISO group, and remained 24-26% lower at 100 days. Early isolation produced no enduring reduction in synaptophysin OD in the amygdala or prefrontal cortex. Overall, these results suggest that early maternal separation produced a regionally specific delayed effect on the structure of the hippocampus by attenuating rates of synaptic development.