title: Effects of chronic stress on structure and cell function in rat hippocampus and hypothalamus.
abstract: It has become increasingly clear that the increase in corticosteroid levels, e.g. after a brief stressor induce molecular and cellular changes in brain, including the hippocampal formation. These effects eventually result in behavioral adaptation. Prolonged exposure to stress, though, may lead to mal-adaptation and even be a risk factor for diseases like major depression in genetically predisposed individuals. We conducted a series of experiments where changes in brain function were examined after 3 weeks of unpredictable stress. After unpredictable stress, inhibitory input to neurons involved in the hypothalamus-pituitary-adrenal (HPA) axis regulation was suppressed, which may dysregulate the axis and lead to overexposure of the brain to glucocorticoids. Furthermore, glutamate transmission in the dentate gyrus (DG) was enhanced, possibly through transcriptional regulation of receptor subunits. Combined with enhanced calcium channel expression this could increase vulnerability to cell death. Neurogenesis and apoptosis in the dentate were diminished. Synaptic plasticity was suppressed both in the dentate and CA1 area. Collectively, these effects may give rise to deficits in memory formation. Finally, we observed reduced responses to serotonin in the CA1 area, which could contribute to the onset of symptoms of depression in predisposed individuals. All of these endpoints provide potential targets for novel treatment strategies of stress-related brain disorders.
authors: SILS-CNS, University of Amsterdam, The Netherlands. joels@science.uva.nl
authors: Marian
authors: M
authors: Joëls
authors: Henk
authors: H
authors: Karst
authors: Deborah
authors: D
authors: Alfarez
authors: Vivi M
authors: VM
authors: Heine
authors: Yongjun
authors: Y
authors: Qin
authors: Els
authors: E
authors: van Riel
authors: Martin
authors: M
authors: Verkuyl
authors: Paul J
authors: PJ
authors: Lucassen
authors: Harm J
authors: HJ
authors: Krugers
mesh_terms: D000818:Animals; D002908:Chronic Disease; D018891:Dentate Gyrus / Q000473:pathology; D005971:Glutamates / Q000502:physiology; D006624:Hippocampus / Q000473:pathology*; D007031:Hypothalamus / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D010286:Paraventricular Hypothalamic Nucleus / Q000473:pathology; D051381:Rats; D013315:Stress, Psychological / Q000473:pathology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D005971:Glutamates; D005680:gamma-Aminobutyric Acid