title: Maternal separation alters nerve growth factor and corticosterone levels but not the DNA methylation status of the exon 1(7) glucocorticoid receptor promoter region.
abstract: Separating rat pups from their mothers during the early stages of life is an animal model commonly used to study the development of psychiatric disorders such as anxiety and depression. The present study investigated how soon after the termination of the maternal separation period behavioural and neuroendocrine abnormalities relevant to above-mentioned illnesses would manifest. Sprague Dawley rat pups were subjected to maternal separation (3 h per day from postnatal day 2 through 14) and their behaviour and HPA axis activity determined 7 d later. We also measured nerve growth factor levels in their hippocampi and assessed the DNA methylation status of the promoter region of exon 1(7) of the glucocorticoid receptor in this brain region. As early as 7 d after the termination of the adverse event, a change in behaviour was observed that was associated with increased plasma corticosterone release and elevated nerve growth factor levels in the hippocampus. No alteration in the methylation status of the exon 1(7) glucocorticoid receptor promoter region was observed. Our data indicate that early life adversity may lead to the rapid development of abnormal behaviours and HPA axis dysregulation though no epigenetic changes to the exon 1(7) glucocorticoid receptor promoter region occurred. We further propose that the observed increased neurotrophin levels reflect compensatory mechanisms that attempt to combat the long-term deleterious effects of maternal separation.
authors.affiliation: Discipline of Human Physiology, Faculty of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa. Danielsw@ukzn.ac.za
authors.forename: W M U
authors.initials: WM
authors.lastname: Daniels
authors.forename: L R
authors.initials: LR
authors.lastname: Fairbairn
authors.forename: G
authors.initials: G
authors.lastname: van Tilburg
authors.forename: C R E
authors.initials: CR
authors.lastname: McEvoy
authors.forename: M J
authors.initials: MJ
authors.lastname: Zigmond
authors.forename: V A
authors.initials: VA
authors.lastname: Russell
authors.forename: D J
authors.initials: DJ
authors.lastname: Stein
mesh_terms: D000818:Animals; D001483:Base Sequence / Q000235:genetics; D001522:Behavior, Animal / Q000502:physiology; D003345:Corticosterone / Q000032:analysis / Q000097:blood*; D019175:DNA Methylation / Q000502:physiology; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic / Q000502:physiology; D005091:Exons / Q000235:genetics; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008426:Maternal Deprivation; D008969:Molecular Sequence Data; D019964:Mood Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D020932:Nerve Growth Factor / Q000032:analysis / Q000097:blood*; D009490:Neurosecretory Systems / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D011965:Receptors, Glucocorticoid; D020932:Nerve Growth Factor; D003345:Corticosterone