title: Increased expression of water channel aquaporin 1 and aquaporin 4 in Creutzfeldt-Jakob disease and in bovine spongiform encephalopathy-infected bovine-PrP transgenic mice.
abstract: Spongiform change is a cardinal feature in transmissible spongiform encephalopathies, including Creutzfeldt-Jakob disease (CJD) and bovine spongiform encephalopathy (BSE). It is characterized by swelling of the neuronal processes and vacuolization of the neuropil, leading to increased intraneuronal water content. The present study examines, by gel electrophoresis and Western blotting, the expression levels of the water channels aquaporin 1 (AQP1) and aquaporin 4 (AQP4) in the frontal cortex (area 8) homogenates of sporadic CJD cases (six men, four women; seven cases with methionine/methionine at codon 129 and PrP type 1; two cases with valine/valine at codon 129 and PrP type 2, and one case methionine/valine at codon 129 and PrP type 1) compared with age-matched controls, and cases with Alzheimer's disease (AD, stage VI of Braak and Braak) and diffuse Lewy body disease (DLB). AQP1 and AQP4 protein levels were also studied in the cerebral cortex of BSE-infected bovine-PrP transgenic mice (BoPrP-Tg110 mice) examined at 60, 150, 210 and 270 days post-inoculation (dpi) compared with healthy brain-inoculated control mice. Quantitative densitometry of AQP bands normalized for beta-actin was analyzed using Statgraphics plus 5.0 software from ANOVA and LSD statistical tests. Significant increased expression levels of AQP1 (as revealed with two different antibodies) and AQP4 were seen in CJD, but not in advanced AD and DLB cases when compared with controls. Immunohistochemistry revealed that AQP1 and AQP4 were expressed in astrocytes in diseased cases. No modifications in the expression levels of AQP1 and AQP4 were observed in BSE-infected bovine-PrP transgenic mice at 60, 150 and 210 dpi. However, a significant increase in the expression levels of AQP1 and AQP4 was found in mice at 270 dpi, the time corresponding with the appearance of PrP(res) immunoreactivity in Western blots and typical spongiform lesions in the brain. Together, these findings show increased expression of water channels in the brain in human and animal prion diseases. These modifications may have implications in the regulation of water transport in astrocytes and may account for an imbalance in water and ion homeostasis in prion diseases.
authors.affiliation: Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Agustín
authors.initials: A
authors.lastname: Rodríguez
authors.forename: Esther
authors.initials: E
authors.lastname: Pérez-Gracia
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Espinosa
authors.forename: Martí
authors.initials: M
authors.lastname: Pumarola
authors.forename: Juan María
authors.initials: JM
authors.lastname: Torres
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D051398:Aquaporin 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051401:Aquaporin 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000378:metabolism*; D016643:Encephalopathy, Bovine Spongiform / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020961:Lewy Body Disease / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D011328:Prions / Q000235:genetics / Q000378:metabolism*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D051401:Aquaporin 4; D005904:Glial Fibrillary Acidic Protein; D011328:Prions; D051398:Aquaporin 1