title: Early maternal separation followed by later stressors leads to dysregulation of the HPA-axis and increases in hippocampal NGF and NT-3 levels in a rat model.
abstract: Early adverse life events, followed by subsequent stressors, appear to increase susceptibility for subsequent onset of psychiatric disorders in humans. The molecular mechanisms that underlie this phenomenon remain unclear, but dysregulation of the HPA axis and alterations in neurotrophic factors have been implicated. The present study investigated the effects in rodents of early maternal separation, followed by stress in adolescence and adulthood on later HPA-axis activity and hippocampal neurotrophin levels (brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3). Animals subjected to repeated stressors showed a significant decrease in basal ACTH (p < 0.05) and CORT (p < 0.05) levels when compared to controls, as well as significantly increased levels of NGF in the dorsal (p < 0.001) and ventral hippocampus (p < 0.01), and of NT-3 in the dorsal hippocampus (p < 0.01). Dysregulation of the HPA axis after multiple stressors is consistent with previous preclinical and clinical work. Given that neurotrophins are important in neuronal survival and plasticity, it is possible to speculate that their elevation reflects a compensatory mechanism.
authors.affiliation: Department of Physiological Sciences, University of Stellenbosch, Stellenbosch, Western Cape, South Africa. jfaure@sun.ac.za
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Faure
authors.forename: Joachim D K
authors.initials: JD
authors.lastname: Uys
authors.forename: Lelanie
authors.initials: L
authors.lastname: Marais
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Stein
authors.forename: Willie M U
authors.initials: WM
authors.lastname: Daniels
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D008426:Maternal Deprivation; D009414:Nerve Growth Factors / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone