title: Decreased glucocorticoid receptor mRNA and dysfunction of HPA axis in rats after removal of the cholinergic innervation to hippocampus.
abstract: Excess exposure to glucocorticoids can have deleterious effects on physiology and cognition. Glucocorticoids acting via receptors located in hippocampal neurons contribute to negative feedback after stress by terminating the further release of glucocorticoids. The current study investigated the effects of selective immunolesions of septo-hippocampal cholinergic neurons on hippocampal corticosterone receptor mRNA and on hypothalamic-pituitary-adrenal (HPA) activity. As evaluated by in situ hybridization, hippocampal glucocorticoid receptor (GR) mRNA, but not mineralocorticoid receptor (MR) mRNA, was significantly decreased in lesioned rats compared to controls. In a companion study, the peak corticosterone response to one hour of restraint stress did not differ between lesion and control groups but the post-stress decline of corticosterone was more protracted in the lesioned rats. These findings are discussed in terms of their possible relevance to ageing as age-related degeneration of the basal forebrain cholinergic system may contribute to the commonly observed dysfunction of the HPA axis in older animals.
authors.affiliation: Department of Psychological and Brain Science, Johns Hopkins University, 3400 North Charles Street, MD 21218, USA. jsh@jhu.edu
authors.forename: Jung-Soo
authors.initials: JS
authors.lastname: Han
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Bizon
authors.forename: Hyun-Ja
authors.initials: HJ
authors.lastname: Chun
authors.forename: Courtney E
authors.initials: CE
authors.lastname: Maus
authors.forename: Michela
authors.initials: M
authors.lastname: Gallagher
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018678:Cholinergic Agents / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D006624:Hippocampus / Q000187:drug effects*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D000922:Immunotoxins / Q000494:pharmacology*; D017403:In Situ Hybridization; D008297:Male; D009699:N-Glycosyl Hydrolases; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020318:Rats, Long-Evans; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013312:Stress, Physiological / Q000378:metabolism
chemical_list: C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D000922:Immunotoxins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D003345:Corticosterone