Maternal deprivation by early weaning increases corticosterone and decreases hippocampal BDNF and neurogenesis in mice.

We previously demonstrated that early weaning increases anxiety and neuroendocrine stress responses in rats and mice. In addition, early-weaned mice show precocious myelin formation, especially in the amygdala, suggesting that these mice are vulnerable to psychological stress. In the present experiments, we examined corticosterone response after early weaning and how early weaning affects hippocampal neurotrophic factor and neurogenesis, which have been linked to depressive behavior in human and animals models. When the mice were weaned at PD14, both male and female mice showed higher corticosterone levels up to 48h after weaning. In contrast, after standard weaning, corticosterone levels returned to the baseline within 2h. Early-weaned males, but not females, had less brain-derived neurotrophic factor (BDNF) protein in the hippocampus at 3 weeks of age than standard-weaned mice. Neural stem cells were labeled with bromodeoxyuridine (BrdU) injections at 2, 3, or 5 weeks of age, and assayed at 3, 5, and 8 weeks of age, respectively. Early-weaned males had fewer BrdU immunoreactive cells in the dentate gyrus at 3, 5, and 8 weeks. In early-weaned females, fewer BrdU-positive cells were observed only at 5 weeks. Double-staining with BrdU and the neuron markers NeuN and Tuj1 demonstrated that neurogenesis was lower in early-weaned mice at 5 weeks of age. These results suggest that lack of mother-infant interaction during the late lactation period leads to an increase in corticosterone synthesis for 2 days and a decrease in BDNF synthesis in males; moreover, this lack of interaction transiently inhibits hippocampal cell proliferation and survival in both males and females, although the effects were more pronounced in males.