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Stress induces equivalent remodeling of hippocampal spine synapses in a simulated postpartum environment and in a female rat model of major depression.

Abstract：

:Stress and withdrawal of female reproductive hormones are known risk factors of postpartum depression. Although both of these factors are capable of powerfully modulating neuronal plasticity, there is no direct electron microscopic evidence of hippocampal spine synapse remodeling in postpartum depression. To address this issue, hormonal conditions of pregnancy and postpartum period were simulated in ovariectomized adult female Sprague-Dawley rats (n=76). The number of hippocampal spine synapses and the depressive behavior of rats in an active escape task were investigated in untreated control, hormone-withdrawn 'postpartum', simulated proestrus, and hormone-treated 'postpartum' animals. After 'postpartum' withdrawal of gonadal steroids, inescapable stress caused a loss of hippocampal spine synapses, which was related to poor escape performance in hormone-withdrawn 'postpartum' females. These responses were equivalent with the changes observed in untreated controls that is an established animal model of major depression. Maintaining proestrus levels of ovarian hormones during 'postpartum' stress exposure did not affect synaptic and behavioral responses to inescapable stress in simulated proestrus animals. By contrast, maintaining pregnancy levels of estradiol and progesterone during 'postpartum' stress exposure completely prevented the stress-induced loss of hippocampal spine synapses, which was associated with improved escape performance in hormone-treated 'postpartum' females. This protective effect appears to be mediated by a muted stress response as measured by serum corticosterone concentrations. In line with our emerging 'synaptogenic hypothesis' of depression, the loss of hippocampal spine synapses may be a novel perspective both in the pathomechanism and in the clinical management of postpartum affective illness.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Baka J,Csakvari E,Huzian O,Dobos N,Siklos L,Leranth C,MacLusky NJ,Duman RS,Hajszan T

doi

10.1016/j.neuroscience.2016.12.021

subject

Has Abstract

pub_date

2017-02-20 00:00:00

pages

384-397

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(16)30711-4

journal_volume

343

pub_type

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Stress induces equivalent remodeling of hippocampal spine synapses in a simulated postpartum environment and in a female rat model of major depression.