Molecular Psychiatry outcome of hormonal changes. Hormones are known to affect adult neurogenesis, even postpartum. 4 However, in a recent study performed by Shingo et al., 8 it was shown that pregnancy-related hormones, such as estrogen and progesterone, have no effect on adult hippocampal neurogenesis, with the exception of prolactin, which directly induces neurogenesis only in the olfactory bulb of pregnant mice. These results led us to consider the possibility that the pregnancyinduced reduction in neurogenesis might not be directly caused by hormonal changes, but rather may be an outcome of other physiological adaptations to pregnancy, such as pregnancy-induced changes in the immune response.

Our group recently showed that the immune system and, in particular, the adaptive immune response contribute to adult hippocampal neurogenesis. 3 During pregnancy, to enable the survival of a fetus, which may be viewed as a semi-allogeneic graft, the immune system undergoes major changes, among them are alternations in T-cell activity. 9 We therefore anticipated that if the pregnancy-induced decrease in neurogenesis is immune-dependent, no reduction in neurogenesis would be observed in immune-deficient mice during pregnancy. We repeated the same experimental paradigm of BrdU injection utilizing nude mice, which lack the entire T-cell population. We observed that in pregnant nude mice, there was only a modest reduction in neurogenesis during pregnancy (Figure 1c). However, when we reconstituted these nude mice with T cells from wild-type mice and mated them 8 days after reconstitution, we were able to restore the pregnancy-induced decrease in neurogenesis (Figure 1c). These results, thus, suggest a dependence of the observed reduction in hippocampal neurogenesis on the presence of T cells; however, the specific contribution of T-cell immunity and the underlying