Prenatal stress and neonatal handling induce sex-specific changes in dendritic complexity and dendritic spine density in hippocampal subregions of prepubertal rats

Abstract

Maternal stress during gestation in humans and experimental animals can result in emotional and cognitive dysfunction in the offspring. To facilitate our understanding of the underlying neuronal changes induced by prenatal stress (PNS), the dendritic and synaptic development was analyzed in three-dimensionally reconstructed Golgi-impregnated neurons in the hippocampal formation of offspring from pregnant dams which were stressed from day 15-20 by varied stressors. The analysis was focused on prepubertal rats and on the comparison of stress vulnerabilities in male and female offspring. In the hippocampal CA1 region PNS increased spine density on pyramidal neurons only in males, which thereby reached the levels observed in control females. On granular neurons of the dentate gyrus, PNS altered spine-density, dendritic length and dendritic complexity in opposite directions in males and females. In the CA3 area, PNS resulted in shorter and less complex dendrites in both sexes compared with unstressed controls. Another aim was to assess whether neonatal environmental interventions, such as handling (H) during the first 10 postnatal days, can reverse PNS-induced neuronal changes. We show here for the first time that H can "reverse" or prevent PNS-induced changes in spine density and dendritic length and complexity in a sex-, region- and dendrite-specific manner. These findings indicate that the sex-specific changes of neuronal and synaptic features in the hippocampal formation may represent a neuronal substrate of the stress-induced behavioral alterations and that these changes can be partly "normalized" by neonatal interventions.