title: The role of glucocorticoid receptor-dependent activity in the amygdala central nucleus and reversibility of early-life stress programmed behavior.
abstract: Early-life stress (ELS) leads to sustained changes in gene expression and behavior, increasing the likelihood of developing a psychiatric disorder in adulthood. The neurobiological basis for the later-in-life psychopathology is relatively unknown. The current study used a mouse model of ELS, achieved by daily maternal separations during the first 2 weeks of postnatal life, to test the role of amygdalar glucocorticoid receptor (GR) function in mediating the persistent increase in risk-taking behaviors. ELS produced a decrease in GR mRNA in the brain, with a notable reduction in the amygdala that was associated with sustained alterations in anxiety, fear and sociability-like behaviors. Lentiviral-mediated restoration of the GR mRNA deficit, specifically within the adult central nucleus of the amygdala (CeA), reversed the enduring changes in anxiety and social behavior after ELS. These results provide evidence of lasting changes in CeA GR neural circuitry following ELS and suggest a mechanistic role for GR-regulated processes in the CeA in mediating the lifelong maladaptive behaviors of ELS. We demonstrate that the long-lasting behavioral effects of ELS are reversible later in life and implicate the involvement of CeA GR-dependent activity in the sustained dysregulation of emotion following ELS.
authors: 1] Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA [2] Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors: M G
authors: MG
authors: Arnett
authors: Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors: M S
authors: MS
authors: Pan
authors: Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors: W
authors: W
authors: Doak
authors: Department of Psychology, Princeton Neuroscience Institute, Princeton, NJ, USA.
authors: P E P
authors: PE
authors: Cyr
authors: Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors: L M
authors: LM
authors: Muglia
authors: 1] Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA [2] Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors: L J
authors: LJ
authors: Muglia
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology*; D066274:Central Amygdaloid Nucleus / Q000378:metabolism*; D004195:Disease Models, Animal; D005239:Fear / Q000502:physiology; D016086:Lentivirus / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012309:Risk-Taking; D013315:Stress, Psychological / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid