Maternal experience inhibits the production of immature neurons in the hippocampus during the postpartum period through elevations in adrenal steroids

Abstract

Motherhood is accompanied by alterations in numerous nonreproductive behaviors, including learning and memory, as well as anxiety and stress regulation. These functions have been linked to adult neurogenesis in the hippocampus, but the effect of maternal experience on this brain region has not been completely explored. To determine whether the production of new hippocampal granule cells is altered during the postpartum period, we examined the number of proliferating cells and their progeny in the dentate gyrus of primiparous female rats at various time points during the postpartum period while they were caring for their offspring, as well as after weaning. Additionally, we investigated whether cell proliferation in the postpartum female is affected by the presence of offspring and nursing-induced increases in glucocorticoids. Analysis of the number of BrdU-labeled cells revealed that cell proliferation in the dentate gyrus was suppressed in lactating postpartum females until the time of weaning. This effect was temporary; a difference was detectable at 1 week after BrdU-labeling, when the majority of cells expressed a marker of immature and mature granule neurons (TuJ1) but not at 2 weeks, when most cells expressed a marker of mature neurons (NeuN). The decrease in cell proliferation was dependent on elevated basal glucocorticoid levels associated with lactation; removal of nursing pups reduced basal corticosterone levels and prevented the decrease in the number of BrdU-labeled cells. Moreover, preventing increased basal corticosterone levels by means of adrenalectomy and low-dose corticosterone replacement eliminated the reduction in cell proliferation. These findings indicate that offspring interactions inhibit adult neurogenesis through changes in adrenal steroids, and further suggest a potential mechanism for alterations in hippocampal function during the postpartum period.

Blood mononuclear cell gene expression signature of postpartum depression

“…Cellular proliferation and survival among neural and glial cells have been implicated in stress-and depressionrelated hippocampal volume depletion, and in some of the protective effects of antidepressant drugs. 44,45 A general decrease in cell proliferation has been shown in the dentate gyrus as early as day 2 postpartum in rodents, 46,47 and has been suggested to contribute to the observed increment in PD incidence. 47 It would be tempting to hypothesize that both the widespread and cell cycle-specific relative reductions in PBMC transcriptional responses observed here among PD patients may mirror a further PD-related accentuation of such a general postpartum temporal reduction in neural and glial cellular capacity for neurogenesis, which has been implicated as an underlying feature of depression pathogenesis.…”

“…44,45 A general decrease in cell proliferation has been shown in the dentate gyrus as early as day 2 postpartum in rodents, 46,47 and has been suggested to contribute to the observed increment in PD incidence. 47 It would be tempting to hypothesize that both the widespread and cell cycle-specific relative reductions in PBMC transcriptional responses observed here among PD patients may mirror a further PD-related accentuation of such a general postpartum temporal reduction in neural and glial cellular capacity for neurogenesis, which has been implicated as an underlying feature of depression pathogenesis. However, all that can be clearly deduced from this data is that the pathwayrelated transcriptional changes observed are robust enough to show a significant appearance among the heterogeneous mononuclear cell composition sampled.…”

Female rats learn trace memories better than male rats and consequently retain a greater proportion of new neurons in their hippocampi

“…The number of cells was multiplied by 24 to obtain an estimate of the total number of BrdU-labeled cells in the hippocampus. To account for sex differences in the size of the hippocampus, we also assessed the total volume of the DG (GCL, SGZ, and hilus) from cross-sectional area measurements obtained with Scion Image software (19,58). The area of the DG was calculated from digital pictures of every twelfth unilateral section throughout the rostrocaudal hippocampus.…”

Impact of diet on adult hippocampal neurogenesis

“…Social isolation is a stressful experience in rodents and has been shown to be another negative regulator of AHN that correlates with learning abilities [69]. Pregnancy [95] and maternal experiences [64] in rodent also have a negative impact on AHN. These are associated with a decline in performance in hippocampus-dependent tasks during pregnancy and the reduced AHN may be an outcome of pregnancy-induced changes in the immune response rather than of hormonal changes [95].…”

“…These are associated with a decline in performance in hippocampus-dependent tasks during pregnancy and the reduced AHN may be an outcome of pregnancy-induced changes in the immune response rather than of hormonal changes [95]. During the postpartum period, the decrease in AHN is dependent on elevated basal glucocorticoid levels [64]. Decreases in AHN during the postpartum period could be linked to postpartum depression experienced by some women.…”