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 myetin 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 mate and female mice showed higher corticosterone levels up to 48 h after weaning. In contrast, after standard weaning, corticosterone levels returned to the baseline within 2 h. Early-weaned mates, 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 mates 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 tower in early-weaned mice at 5 weeks of age. These results suggest that tack 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 mates; moreover, this lack of interaction transiently inhibits hippocampal cell proliferation and survival in both mates and females, although the effects were more pronounced in mates. (C) 2008 Elsevier Ltd. All rights reserved.