Abstract
BackgroundPostpartum depression affects approximately 15% of mothers and represents a form of early life adversity for developing offspring. Postpartum depression can be treated with prescription antidepressants like fluoxetine (FLX). However, FLX can remain active in breast milk, raising concerns about the consequences of neonatal FLX exposure. The hippocampus is highly sensitive to developmental stress, and males and females respond differently to stress at many endpoints, including hippocampal plasticity. However, it is unclear how developmental exposure to FLX alters the trajectory of hippocampal development. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum depression) and concurrent FLX on hippocampal neurogenesis in male and female offspring.MethodsFemale Sprague-Dawley rat dams were treated daily with either CORT or oil and FLX or saline from postpartum days 2–23. Offspring were perfused on postnatal day 31 (pre-adolescent), postnatal day 42 (adolescent), and postnatal day 69 (adult). Tissue was processed for doublecortin (DCX), an endogenous marker of immature neurons, in the dorsal and ventral hippocampus.ResultsMaternal postpartum CORT reduced density of DCX-expressing cells in the dorsal hippocampus of pre-adolescent males and increased it in adolescent males, suggesting that postpartum CORT exposure disrupted the typical progression of the density of DCX-expressing cells. Further, among offspring of oil-treated dams, pre-adolescent males had greater density of DCX-expressing cells than pre-adolescent females, and maternal postpartum CORT prevented this sex difference. In pre-adolescent females, maternal postpartum FLX decreased the density of DCX-expressing cells in the dorsal hippocampus compared to saline. As expected, maternal CORT reduced the density of DCX-expressing cells in adult female, but not male, offspring. The combination of maternal postpartum CORT/FLX diminished density of DCX-expressing cells in dorsal hippocampus regardless of sex or age.ConclusionsThese findings reveal how modeling treatment of postpartum depression with FLX alters hippocampal neurogenesis in developing offspring differently depending on sex, predominantly in the dorsal dentate gyrus and earlier in life.
Highlights
Postpartum depression affects approximately 15% of mothers and represents a form of early life adversity for developing offspring
Dorsal versus ventral hippocampus: maternal postpartum CORT and/or FLX affect density of immature neurons respond differently depending on sub-region In the present study, we found that neurogenesis in the dorsal hippocampus was more sensitive to maternal treatments with CORT or FLX than in the ventral hippocampus and that when concurrent of both drugs had opposing effects in dorsal and ventral hippocampus regardless of age or sex
Collectively, these findings highlight that males and females are differentially vulnerable at different time periods during development to the effects of maternal postpartum CORT and/or maternal postpartum FLX
Summary
Postpartum depression affects approximately 15% of mothers and represents a form of early life adversity for developing offspring. Maternal SSRI use has been linked to delayed psychomotor development in infants [9], increased internalizing behavior in children (i.e., behaviors predisposing anxiety and depression; [10]), and a higher risk for autism spectrum disorders in children [11] These findings may be consistent with preclinical findings from our laboratory that maternal postpartum fluoxetine (FLX) exposure increased anxiety-like behavior in young adult male offspring [12]. As in the clinical literature, preclinical research has yielded mixed results regarding maternal SSRI exposure on offspring outcome depending on whether a model of concurrent maternal depression was used, sex of the offspring studied, and age examined (reviewed in [13]) To this end, this study aims to contribute a better understanding of how maternal SSRI exposure in a rat model of PPD affects male and female development ( hippocampal neurogenesis) at three different ages
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