title: Effects of cholinergic lesions produced by infusions of 192 IgG-saporin on glucocorticoid receptor mRNA expression in hippocampus and medial prefrontal cortex of the rat.
abstract: Principal neurons in the hippocampus and prefrontal cortex of the rat have been identified as targets for glucocorticoids involved in the hypothalamic-pituitary-adrenocortical stress response. Alterations in mRNA expression for glucocorticoid receptors in each of these regions have been shown to affect the negative feedback response to corticosterone following an acute stressor. Both decreases in forebrain glucocorticoid receptors and in the efficiency of adrenocortical feedback have been observed in normal aging, and have been selectively induced with experimental lesions or manipulations in neurotransmitter systems. The current study investigated the possibility that a loss of cholinergic support from cells in the basal forebrain, a hallmark of aging, contributes to the selective age-related loss of glucocorticoid receptor mRNA expression at cholinoceptive target sites that include the hippocampus and medial prefrontal cortex. Lesions of the basal forebrain cholinergic system in young adult rats were made by microinjections of the immunotoxin 192 IgG-saporin into the medial septum/vertical limb of the diagonal band and substantia innominata/nucleus basalis. Basal levels of circulating glucocorticoids were unaffected by the lesions. Analysis of both mineralocorticoid and glucocorticoid receptor mRNA expression revealed a significant decrease in glucocorticoid receptor mRNA in the hippocampus and medial prefrontal cortex, with spared expression at subcortical sites and no detectable change in mineralocorticoid receptor mRNA in any of the examined regions. Thus, rats with lesions of the basal forebrain cholinergic system recapitulate some of the detrimental effects of aging associated with glucocorticoid-mediated stress pathways in the brain.
authors.affiliation: Department of Psychological and Brain Sciences, The Johns Hopkins University, 3400 North Charles Street, Ames Hall, Baltimore, MD 21218, USA. kassie@jhu.edu
authors.forename: K A
authors.initials: KA
authors.lastname: Helm
authors.forename: J-S
authors.initials: JS
authors.lastname: Han
authors.forename: M
authors.initials: M
authors.lastname: Gallagher
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D020532:Basal Nucleus of Meynert / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D003714:Denervation; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology; D000922:Immunotoxins / Q000494:pharmacology; D008297:Male; D009699:N-Glycosyl Hydrolases; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology
chemical_list: C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D000109:Acetylcholine; D003345:Corticosterone