title: Chronic stress prior to pregnancy potentiated long-lasting postpartum depressive-like behavior, regulated by Akt-mTOR signaling in the hippocampus.
abstract: Postpartum depression (PPD) affects over 10% of new mothers and adversely impacts the health of offspring. One of the greatest risk factors for PPD is prepregnancy stress but the underlying biological mechanism is unknown. Here we constructed an animal model which recapitulated prepregnancy stress induced PPD and tested the role of Akt-mTOR signaling in the hippocampus. Female virgin Balb/c mice received chronic restraint stress, followed by co-housing with a normal male mouse. We found that the chronic stress led to a transient depressive-like condition that disappeared within two weeks. However, prepregnantly stressed females developed long-term postpartum depressive-like (PPD-like) symptoms as indicated by deficient performance in tests of sucrose preference, forced swim, and novelty-suppressed feeding. Chronic stress induced transient decrease in Akt-mTOR signaling and altered expressions of glutamate receptor subunits NR1 and GluR1, in contrast to long-term deficits in Akt-mTOR signaling, GluR1/NR1 ratio, and hippocampal neurogenesis in PPD-like mice. Acute ketamine improved the molecular signaling abnormality, and reversed the behavioral deficits in PPD-like mice in a rapid and persistent manner, in contrast to ineffectiveness by chronic fluoxetine treatment. Taken together, we find that chronic prepregnancy stress potentiates a long-term PPD, in which Akt-mTOR signaling may play a crucial role.
authors.affiliation: Center for Translational Systems Biology and Neuroscience, and Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Faculty of Rehabilitation Science, Nanjing Normal University of Special Education, Nanjing, 210023, China.
authors.forename: Baomei
authors.initials: B
authors.lastname: Xia
authors.affiliation: Encephalopathy department, The Third Affiliated Hospital of Nanjing University of Chinese medicine, Nanjing, 210001, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Chen
authors.affiliation: Center for Translational Systems Biology and Neuroscience, and Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors.forename: Hailou
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Center for Translational Systems Biology and Neuroscience, and Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors.forename: Wenda
authors.initials: W
authors.lastname: Xue
authors.affiliation: Center for Translational Systems Biology and Neuroscience, and Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Tang
authors.affiliation: Center for Translational Systems Biology and Neuroscience, and Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Tao
authors.affiliation: Center for Translational Systems Biology and Neuroscience, and Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors.forename: Ruyan
authors.initials: R
authors.lastname: Wu
authors.affiliation: Center for Translational Systems Biology and Neuroscience, and Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ren
authors.affiliation: School of Psychology, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Center for Translational Systems Biology and Neuroscience, and Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D019052:Depression, Postpartum / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D020890:Neuregulin-1 / Q000378:metabolism; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013315:Stress, Psychological / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D007649:Ketamine; D020890:Neuregulin-1; D051057:Proto-Oncogene Proteins c-akt; D018091:Receptors, AMPA; D058570:TOR Serine-Threonine Kinases; C094131:NRG1 protein, human; C546842:MTOR protein, human