title: 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synapses and the depressive behavior of rats in an active escape task were investigated in untreated control, hormone-withdrawn 'postpartum', simulated proestrus, and hormone-treated 'postpartum' animals.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inescapable stress caused a loss of hippocampal spine synapses, which was related to poor escape performance in hormone-withdrawn 'postpartum' females.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.
authors.affiliation: Institute of Biophysics, Biological Research Center, Hungarian Academy of Sciences, Temesvari Krt 62, 6726 Szeged, Hungary.
authors.forename: Judith
authors.initials: J
authors.lastname: Baka
authors.affiliation: Institute of Biophysics, Biological Research Center, Hungarian Academy of Sciences, Temesvari Krt 62, 6726 Szeged, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Csakvari
authors.affiliation: Institute of Biophysics, Biological Research Center, Hungarian Academy of Sciences, Temesvari Krt 62, 6726 Szeged, Hungary.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Huzian
authors.affiliation: Institute of Biophysics, Biological Research Center, Hungarian Academy of Sciences, Temesvari Krt 62, 6726 Szeged, Hungary.
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Dobos
authors.affiliation: Institute of Biophysics, Biological Research Center, Hungarian Academy of Sciences, Temesvari Krt 62, 6726 Szeged, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Siklos
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, United States; Department of Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, United States.
authors.forename: Csaba
authors.initials: C
authors.lastname: Leranth
authors.affiliation: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 50 Stone Road E, Guelph, Ontario N1G 2W1, Canada.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: MacLusky
authors.affiliation: Department of Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, United States; Department of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, United States.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Duman
authors.affiliation: Institute of Biophysics, Biological Research Center, Hungarian Academy of Sciences, Temesvari Krt 62, 6726 Szeged, Hungary; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, United States. Electronic address: hajszan.tibor@brc.mta.hu.
authors.forename: Tibor
authors.initials: T
authors.lastname: Hajszan
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood; D019052:Depression, Postpartum / Q000378:metabolism / Q000473:pathology*; D003865:Major Depressive Disorder / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D009473:Neuronal Plasticity / Q000502:physiology; D010052:Ovariectomy; D049590:Postpartum Period; D011359:Proestrus / Q000502:physiology; D011374:Progesterone / Q000008:administration & dosage / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism / Q000473:pathology*
chemical_list: D011374:Progesterone; D004958:Estradiol; D003345:Corticosterone
keywords: electron microscopy; estradiol; plasticity; postpartum depression; progesterone; stress