title: Prominent corticosteroid disturbance in experimental prion disease.
abstract: Prion diseases comprise a group of neurodegenerative disorders that invariably lead to death in affected individuals. The most prominent event in these diseases is a rapid and pronounced neuronal loss, although the cause and the precise mechanisms of neuronal cell death have not been identified so far. Recently, it has been suggested that corticosteroids might play a role in the pathogenesis of neurodegenerative disorders in general, as the regulation of these hormones was found to be disturbed in Alzheimer's and Parkinson's disease, as well as in a transgenic mouse model of Alzheimer's disease. To evaluate the possible corticosteroid disturbances in prion diseases, we determined the concentration of corticosterone metabolites in the faeces of scrapie-inoculated mice during the course of the clinical disease. We observed markedly elevated concentrations of the metabolites during the last 5 weeks of the disease, as well as a severe disturbance of circadian periodicity of corticosterone excretion as much as 2 weeks before this elevation. A simultaneous downregulation of cerebral neuronal glucocorticoid receptors was not detectable by immunohistochemistry, indicating that increased corticosteroids can elicit their effects in mouse scrapie freely. The dysregulation of corticosteroid excretion might act as a further cofactor in the pathogenesis of scrapie, for example by preconditioning nerve cells to disease-immanent neurotoxic stimuli, such as oxidative stress, and to apoptosis.
authors.affiliation: Institute of Neurology, Medical University of Vienna, AKH, Währinger Gürtel 18-20, A-1097 Vienna, Austria. till.voigtlaender@meduniwien.ac.at
authors.forename: Till
authors.initials: T
authors.lastname: Voigtländer
authors.forename: Ursula
authors.initials: U
authors.lastname: Unterberger
authors.forename: Chadi
authors.initials: C
authors.lastname: Touma
authors.forename: Rupert
authors.initials: R
authors.lastname: Palme
authors.forename: Brigitte
authors.initials: B
authors.lastname: Polster
authors.forename: Michaela
authors.initials: M
authors.lastname: Strohschneider
authors.forename: Susanna
authors.initials: S
authors.lastname: Dorner
authors.forename: Herbert
authors.initials: H
authors.lastname: Budka
mesh_terms: D000305:Adrenal Cortex Hormones / Q000032:analysis* / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology; D004195:Disease Models, Animal; D005243:Feces / Q000737:chemistry; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D017096:Prion Diseases / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism
chemical_list: D000305:Adrenal Cortex Hormones; D011965:Receptors, Glucocorticoid