Sex-dependent Effects of Maternal Corticosterone and SSRI Treatment on Hippocampal Neurogenesis Across Development

Overview

Journal Biol Sex Differ

Publisher Biomed Central

Specialties Biology
Physiology

Date 2017 Jun 6

PMID 28580124

Citations 10

Authors

Aarthi R Gobinath

Joanna L Workman

Carmen Chow

Stephanie E Lieblich

Liisa A M Galea

Affiliations

Soon will be listed here.

Abstract

Background: Postpartum 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.

Methods: Female 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.

Results: Maternal 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.

Conclusions: These 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.

Citing Articles

Corticosterone-induced postpartum depression induces depression-like behavior and impairs hippocampal neurogenesis in adolescent offspring via HPA axis and BDNF-mTOR pathway.

Xie H, Jiang Y, Zhang X, Min X, Zeng J, Chen L Neurobiol Stress. 2025; 34:100708.

PMID: 39877695 PMC: 11772995. DOI: 10.1016/j.ynstr.2025.100708.

Male Stressed Mice Having Behavioral Control Exhibit Escalations in Dorsal Dentate Adult-Born Neurons and Spatial Memory.

Sun L, Liao Y, Chan Y, Yu A, Wu C, Kuo I Int J Mol Sci. 2023; 24(3).

PMID: 36768303 PMC: 9916676. DOI: 10.3390/ijms24031983.

Profiling placental DNA methylation associated with maternal SSRI treatment during pregnancy.

Inkster A, Konwar C, Penaherrera M, Brain U, Khan A, Price E Sci Rep. 2022; 12(1):22576.

PMID: 36585414 PMC: 9803674. DOI: 10.1038/s41598-022-26071-8.

Involvement of Intestinal Microbiota in Adult Neurogenesis and the Expression of Brain-Derived Neurotrophic Factor.

Agnihotri N, Mohajeri M Int J Mol Sci. 2022; 23(24).

PMID: 36555576 PMC: 9783874. DOI: 10.3390/ijms232415934.

Maternal Neu5Ac Supplementation During Pregnancy Improves Offspring Learning and Memory Ability in Rats.

Bian D, Wang X, Huang J, Chen X, Li H Front Nutr. 2021; 8:641027.

PMID: 34722600 PMC: 8548574. DOI: 10.3389/fnut.2021.641027.

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