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Publication : Age- and sex-dependent development of adrenocortical hyperactivity in a transgenic mouse model of Alzheimer's disease.

First Author  Touma C Year  2004
Journal  Neurobiol Aging Volume  25
Issue  7 Pages  893-904
PubMed ID  15212843 Mgi Jnum  J:101683
Mgi Id  MGI:3604818 Doi  10.1016/j.neurobiolaging.2003.09.004
Citation  Touma C, et al. (2004) Age- and sex-dependent development of adrenocortical hyperactivity in a transgenic mouse model of Alzheimer's disease. Neurobiol Aging 25(7):893-904
abstractText  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.
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