title: Chronic Postnatal Stress Induces Depressive-like Behavior in Male Mice and Programs second-Hit Stress-Induced Gene Expression Patterns of OxtR and AvpR1a in Adulthood.
abstract: Chronic stress (CS) during early life represents a major risk factor for the development of mental disorders, including depression. According to the Two/Multiple-Hit hypothesis, the etiology of neuropsychiatric disorders usually involves multiple stressors experienced subsequently during different phases of life. However, the molecular and cellular mechanisms modulating neuronal and behavioral changes induced by multiple stress experiences are just poorly understood. Since the oxytocinergic and vasopressinergic systems are neuroendocrine modulators involved in environmentally driven adaptations of stress sensitivity we hypothesized that postnatal CS programs oxytocinergic and vasopressinergic receptor expression changes in response to a second stress exposure in young adulthood. First we investigated if postnatal CS (maternal separation + social isolation) induces depressive-like behavior and alters oxytocin receptor (OxtR) and arginine vasopressin receptor type 1a (AvpR1a) gene expression in the hippocampus (HC) of male mice and (2) if a second single stressor (forced swimming, FS) in young adulthood affects gene expression of OxtR and AvpR1a at adulthood dependent on CS pre-experience. We found that postnatal CS induced depressive-like behavior and enhanced AvpR1a expression in HC at young adulthood. Moreover, in line with our hypothesis, only combined stress exposure (CS + FS), but not CS or FS alone, resulted in increased gene expression of OxtR in HC at adulthood. In contrast, AvpR1a expression was decreased in both adult FS and CS + FS animals. Overall, our results provide evidence that CS programs neuroendocrine systems and thereby influences stress responses in later life periods.
authors.affiliation: Department of Zoology and Developmental Neurobiology, Institute of Biology, Otto von Guericke University, Magdeburg, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lesse
authors.affiliation: Department of Zoology and Developmental Neurobiology, Institute of Biology, Otto von Guericke University, Magdeburg, Germany.
authors.forename: Kathy
authors.initials: K
authors.lastname: Rether
authors.affiliation: Department of Zoology and Developmental Neurobiology, Institute of Biology, Otto von Guericke University, Magdeburg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Gröger
authors.affiliation: Department of Zoology and Developmental Neurobiology, Institute of Biology, Otto von Guericke University, Magdeburg, Germany.|Center for Behavioral Brain Science, Otto von Guericke University, Magdeburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Braun
authors.affiliation: Department of Zoology and Developmental Neurobiology, Institute of Biology, Otto von Guericke University, Magdeburg, Germany. joerg.bock@ovgu.de.|Center for Behavioral Brain Science, Otto von Guericke University, Magdeburg, Germany. joerg.bock@ovgu.de.|Research Group Epigenetics & Structural Plasticity, Institute of Biology, Otto von Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany. joerg.bock@ovgu.de.
authors.forename: Jörg
authors.initials: J
authors.lastname: Bock
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D002755:Choice Behavior; D002908:Chronic Disease; D003863:Depression / Q000209:etiology* / Q000235:genetics*; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008426:Maternal Deprivation; D008810:Mice, Inbred C57BL; D018045:Receptors, Oxytocin / Q000235:genetics* / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000235:genetics* / Q000378:metabolism; D012934:Social Isolation; D013315:Stress, Psychological / Q000150:complications*; D013550:Swimming
chemical_list: D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin
keywords: Depression; Early-life stress; Limbic; Neuropeptide; Two-hit