title: Rosiglitazone reverses memory decline and hippocampal glucocorticoid receptor down-regulation in an Alzheimer's disease mouse model.
abstract: Clinical trials with rosiglitazone, a potent agonist at peroxisome proliferator-activated receptor gamma (PPARgamma) suggest an improvement of cognitive function in Alzheimer's disease (AD) patients. The mechanisms mediating this potential beneficial effect remain to be fully elucidated. In mice overexpressing mutant human amyloid precursor protein (hAPP), a model of AD, we found that memory impairment in the object recognition test was prevented and also reversed by chronic rosiglitazone treatment. Given the possible involvement of glucocorticoid receptors (GR) in the actions of PPARgamma-ligands, we studied the effect of chronic rosiglitazone treatment on GR levels in the hippocampus of hAPP mice. An early down-regulation of GR, not related to elevated plasma corticosterone levels, was found in different hippocampal subfields of the transgenic mice and this decrease was prevented by rosiglitazone. In parallel with behavioural studies, rosiglitazone also normalized GR levels in older animals. This effect may contribute to explain the attenuation of memory decline by PPARgamma activation in an AD mouse model.
authors.affiliation: Division of Neurosciences, CIMA, University of Navarra, Av. Pio XII 55, 31008 Pamplona, CIBERNED, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Escribano
authors.forename: Ana-María
authors.initials: AM
authors.lastname: Simón
authors.forename: Alberto
authors.initials: A
authors.lastname: Pérez-Mediavilla
authors.forename: Pablo
authors.initials: P
authors.lastname: Salazar-Colocho
authors.forename: Joaquín
authors.initials: J
authors.lastname: Del Río
authors.forename: Diana
authors.initials: D
authors.lastname: Frechilla
mesh_terms: D000284:Administration, Oral; D000544:Alzheimer Disease / Q000097:blood / Q000150:complications* / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015536:Down-Regulation; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008569:Memory Disorders / Q000097:blood / Q000235:genetics / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000097:blood / Q000378:metabolism*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D016564:Amyloid beta-Protein Precursor; D047495:PPAR gamma; D011965:Receptors, Glucocorticoid; D045162:Thiazolidinediones; D000077154:Rosiglitazone