title: Age- and sex-dependent development of adrenocortical hyperactivity in a transgenic mouse model of Alzheimer's disease.
abstract: In this study, we investigated mice of the TgCRND8 line, an APP transgenic mouse model of Alzheimer's disease (AD), with respect to behavioral, endocrinological, and neuropathological parameters. Our results show that transgenic and wild-type mice did not differ in their general health status, exploratory and anxiety related behavior as well as in the activity of their sympathetic-adrenomedullary system. Significant differences, however, were found regarding body weight, amyloid plaque formation, and the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis. Continuous monitoring of glucocorticoid (GC) concentrations over a period of 120 days, utilizing a noninvasive technique to measure corticosterone metabolites in fecal samples, revealed that transgenic animals showed adrenocortical hyperactivity, starting very early in males (from day 30) and later in females (around day 90). It is hypothesized that these changes in the activity of the HPA axis are linked to amyloid-beta associated pathological alterations in the hippocampus, causing degenerations in the negative feedback regulation of the HPA axis leading to hypersecretion of GC. Thus, the development of adrenocortical hyperactivity might be a key-element in the understanding of AD.
authors.affiliation: Department of Behavioural Biology, University of Muenster, Badestrasse 9, D-48149 Muenster, Germany. touma@uni-muenster.de
authors.forename: Chadi
authors.initials: C
authors.lastname: Touma
authors.forename: Oliver
authors.initials: O
authors.lastname: Ambrée
authors.forename: Nicole
authors.initials: N
authors.lastname: Görtz
authors.forename: Kathy
authors.initials: K
authors.lastname: Keyvani
authors.forename: Lars
authors.initials: L
authors.lastname: Lewejohann
authors.forename: Rupert
authors.initials: R
authors.lastname: Palme
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
authors.forename: Katja
authors.initials: K
authors.lastname: Schwarze-Eicker
authors.forename: Norbert
authors.initials: N
authors.lastname: Sachser
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D000682:Amyloid / Q000096:biosynthesis* / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000503:physiopathology; D001835:Body Weight / Q000235:genetics / Q000502:physiology*; D003345:Corticosterone / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D006224:Cricetinae; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005243:Feces / Q000737:chemistry; D005260:Female; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D058225:Plaque, Amyloid / Q000473:pathology; D012737:Sex Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D014446:Tyrosine 3-Monooxygenase; D003345:Corticosterone